Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. The main risks considered in this study are infections by West Nile virus, dengue virus and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of Public Health, which is responsible for issuing guidelines to mitigate the risks associated with products of human origin and for supporting public health policy decisions, are briefly outlined. The aim of this review is also to contribute to the standardization of recommendations at international level in areas with the same viral epidemiology.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from the patients’ bodies. A potential strategy called “lock-in apoptosis” targeting the budding phase of life cycle of virus leading to susceptibility to apoptosis of HIV-1 infected cells for elimination of HIV-1 reservoirs and ultimately for a complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA) approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

Due to the fact that to date, the question of the origin of SARS-CoV-2 has not been resolved yet, the author analyzed the main advances in the development of genetic engineering of viruses that took place before the onset of the COVID-19 pandemic. The first artificial genetically modified viruses could appear in nature in the mid-1950s. The technique of nucleic acid hybridization was developed by the end-1960s. In the late 1970s, a method called the "reverse genetics" emerged to synthesize RNA and DNA molecules. In the early 1980-s, it became possible to combine the genes of different viruses and insert the genes of one virus into the genome of another virus. Since that time, the production of vector vaccines began. Currently, by modern technologies one can assemble any virus based on the nucleotide sequence available in the virus database or designed by a computer as a virtual model.Scientists around the world are invited to answer the call of Neil Harrison and Jeffrey Sachs of Columbia University, for a thorough and independent investigation into the origin of SARS-CoV-2. Only a full understanding of the origin of the new virus can minimize the likelihood of a similar pandemic in the future.

We present the detailed calculations of social distancing requirement. A comparative study of the growth pattern and death tolls in different communities indicates that the growth pattern of infected patients and death rate follow the similar distribution with different parametrizations. Every distribution follows an exponential growth pattern curve, like other microbes, then reaches the saturation point an d eventually decay s However, the argument for the exponential function depends on several parameters unbeknownst, as of yet. However, the slope varies different ial ly for various epicenter s and seems to have a relationship with parameters such as accessibi lity to healthcare facilities, pre existing medical conditions socio economic conditions and lifestyle. The mismatch of the growth pattern is also linked with the impact of various other factors and a premature interpretation of limit ed data. Novel behavi or of the virus brought many surprises, opened up new venues for medical research, and the need for the more detailed study of pathogens in the light of the interaction of RNA and DNA The adaptability to diverse ecological condition s and the relevant modification in the structure is also worth investigation The genetic modification can be studied using quantum mechanical probabilistic approach.

Infection with human immunodeficiency virus (HIV) and induced acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst the HAART regimens, darunavir and atazanavir in terms of protease inhibitors, tenofovir disoproxil fumarate, nevirapine or rilpivirine in terms of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors respectively, and especially integrase inhibitors, have demonstrated the most favorable lipid profile emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

In a single-center, retrospective study, 22 cases were enrolled and divided into two groups: those who underwent surgical wide excision (group A) and those who did not (group B). The study included 13 cases in group A and 9 cases in group B. In group A, 6 cases solely underwent surgical wide excision, while 7 cases received additional treatments like radiotherapy or chemotherapy. Conversely, in group B, 4 cases received chemotherapy, 4 cases received radiotherapy, and 1 case was managed through observation alone. The mean follow-up time was 60.15 months in group A and 43.44 months in group B, with no significant difference observed. In group A, 9 cases resulted in mortality, whereas 6 cases died within the follow-up period in group B. Lesion-free intervals post-operation were observed predominantly in group A, while 7 cases in group B never experienced freedom from skin lesions. Kaplan-Meier survival curve analysis demonstrated a significant difference between the survival curves of the two groups (P = 0.046). Among non-HIV Kaposi’s sarcoma patients, surgical wide excision appears to have a role in treatment. Patients in group A exhibit a more favorable outcome in the survival curve analysis.

There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4+ T-cell counts, reverses immunodeficiency, and increases life expectancy. Despite these substantial advances, ART is a lifelong treatment for people with HIV (PWH) and upon cessation or interruption, the virus quickly rebounds in plasma and anatomic sites including the central nervous system (CNS), resulting in disease progression. With recent advances in quantifying viral burden, detection of genetically intact viral genomes, and isolation of replication-competent virus from brain tissues of PWH receiving ART, it has become apparent that the CNS viral reservoir (largely comprised of macrophage type cells) poses a substantial challenge for HIV cure strategies. Other obstacles impacting the cure of HIV include ageing populations, substance use, comorbidities, limited antiretroviral drug efficacy in CNS cells and ART-associated neurotoxicity. Herein, we review recent findings including studies of the proviral integration sites, reservoir decay rates, and new treatment/prevention strategies in the context of the CNS, together with highlighting the next steps for investigations of the CNS as a viral reservoir.

As of the end of 2022, despite the disruptions caused by the COVID-19 pandemic, the global HIV epidemic persists, with 39 million individuals living with the virus and 1.3 million new infections reported in that year. Opportunistic infections associated with AIDS claimed the lives of over 630,000 people in 2022, contributing to a cumulative death toll exceeding 40.4 million since the disease's emergence in 1981. Although advances in HIV diagnosis and antiretroviral therapy have transformed the disease into a manageable chronic condition, issues like drug resistance, low compliance, and high treatment costs persist. Until a vaccine becomes available, a comprehensive approach involving prevention and therapy is essential, particularly for high-risk populations. Research shows that prevention strategies are more cost-effective than treatment. The development of antiretroviral drugs has also spurred the creation of antivirals for other infections. The emergence of COVID-19 vaccines has opened new avenues for HIV vaccine development, as lessons from vaccine platform technologies like mRNA, viral vectors, and protein subunits can be applied to HIV. This review explores the most promising prophylactic and therapeutic HIV vaccine trials, emphasizing the need for a multi-pronged approach combining vaccines with non-vaccine strategies. Though significant progress is anticipated, the road to a viable HIV vaccine remains long, especially for high-risk populations, such as medical workers, blood transfusion recipients, and drug users. The combinatorial approach, capitalizing on various aspects of immunity, may hold the key to defeating HIV in the future.

The human interferon-induced transmembrane (IFITM) proteins inhibit the fusion of a broad spectrum of enveloped viruses, both when expressed in target cells and when present in infected cells. Upon expression in infected cells, IFITMs incorporate into progeny virions and reduce their infectivity by a poorly understood mechanism. Since only a few Env glycoproteins are present on HIV-1 particles, and Env clustering has been proposed to be essential for optimal infectivity, we asked if IFITM protein incorporation modulates HIV-1 Env clustering. The incorporation of two members of the IFITM family, IFITM1 and IFITM3, into HIV-1 pseudoviruses verified by Western blotting correlated with a marked reduction of infectivity. Super-resolution imaging of Env distribution on single HIV-1 pseudoviruses did not reveal significant effects of IFITMs on Env clustering. However, IFITM3 markedly reduced the Env processing and incorporation into virions relative to control and IFITM1-containing viruses. These results suggest that IFITM1 and IFITM3 restrict progeny HIV-1 infectivity via distinct mechanisms. We propose that IFITM1 interferes with viral fusion by altering the properties of the viral membrane or Env functionality by means other than disrupting Env clusters, while IFITM3 also targets Env processing and incorporation into progeny virions.

Intimate partner violence (IPV), particularly sexual and emotional violence, against Black mothers who acquire human immunodeficiency virus (HIV) during childbearing age is a significant health and social concern worldwide requiring targeted interventions and precautions. IPV against women increases the chances of early mixed feeding, putting infants at high risk of mother-to-child transmission of HIV and increased infant morbidities. Although violence complicates many Black mothers’ lives, there is limited research evidence about the critical intersections of violence, HIV, and Black motherhood. Women's fears associated with IPV make them less likely to disclose their positive HIV status to their partners which subsequently prevents them from using the recommended guidelines for safe infant feeding practices. This review aims to explore the critical intersections between IPV and HIV and the impact of both on the infant feeding practices of Black mothers living with HIV. Furthermore, the theme of IPV and how it overlaps with other factors such as HIV-positive status and gender dynamics to compromise the Black motherhood experience are the focus of this narrative review of existing literature. Understanding the intersection of IPV and other factors influencing infant feeding practices among women living with HIV will help inform programming and policy interventions for HIV-positive Black mothers who may be experiencing IPV during the perinatal period.

Aims: The aims of this meta-analysis were to assess: the prevalence of Post-Acute COVID-19 sequalae in HIV positive patients; average time of diagnosis; and meta-regress for possible moderators of PACS.Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database to get the best relevant results. These included Medline indexed journals; PubMed Central; NCBI Bookshelf and publishers' Web sites in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included “long COVID-19 or post-acute COVID-19 syndrome/sequalae”, “persons living with HIV or HIV. The criteria for inclusion were published clinical articles reporting HIV in association with long COVID-19, further, the average time to an event of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Egger's tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The review/trial was PROSPERO registered (CRD42022328509).Results: A total of 43 studies reported post-acute COVID-19 syndrome. Of those, five reported post-acute COVID-19 sequalae in PLHIV. Prevalence of post-acute COVID-19 sequalae was 43.1% (95% CI 20.5% to 68.9%) in persons living with HIV (PLWH). The average time to PACS diagnosis was 4 months at 64% [0.64 (95% CI 0.230, 0.913) (P < 0.0000), I²= 93%] and at one year to PACS diagnosis was at 70 %, however with non-significant correlation (P > 0.05). On comorbidities, asthenia was associated with PACS at 17.6 % [0.176 (95% CI 0.067, 0.385) (P = 0.008), I²= 86%] while fatigue at 82%, however not related with PACS event incidence (P < 0.05). Americas, Asian and European regions showed PACS events rates of 82%, 43% and 19 % respectively (P<0.05) relative to HIV infection. Conclusion: PACS prevalence in PLWH was 43% occurring at an average time of 4 months at 64% and 70 % at 12 months however non-significant with PACS. Asthenia was significantly associated with PACS at 17.6 % while fatigue at 82%, however not related with PACS event incidence. Americas recorded the highest PACS event rates in PLWH.

: Background and objectives: One of the most severe symptoms of extrapulmonary tuberculosis (TBEP) is tuberculous meningitis (TBM) which is linked to significant morbidity and high mortality. It is well recognized that HIV-positive people are more likely to develop TBEP, including TBM, especially if they have severe immunodeficiencies. Material and methods: We conducted a retrospective clinical study based on hospital medical records of the diagnosed patients with HIV/AIDS and Tuberculous Meningitis in North-eastern Romania, hospitalized at "Sf. Parascheva" Clinical Hospital of Infectious Diseases from Iasi. We aim to highlight the profile and the caracteristics of the HIV/AIDS and Tuberculous Meningitis coinfection cases. The time frame under study was from January 1st, 2010, to December 1st, 2022. Results: Our Center has a total number of patients on record of 1692. Patients co-infected with HIV- TB were 195 of which 19 cases were HIV- TBM coinfection and it was more common in women. From this total, 6 cases were late presenters and 13 patients were already in the center's records with a deficient immunological viral status, non-compliant, and non-adherent to antiretroviral therapy. The average age in the study group was 27 years old. The mean admission day number was 17.73 days. CSF findings (qualitative and quantitaitve examination, biochemestry) were in accordance with the literature. Conclusions: The key to the management of the HIV-positive patient is the multidisciplinary approach and access to antiretroviral therapy. We must find and eliminate obstacles affecting patients and the healthcare system. In order to increase ART uptake among HIV-infected TB patients and to put an end to the TB and HIV epidemics.

Cryptococcosis is a leading cause of death among people with HIV in sub-Saharan Africa. Limited diagnostic and therapeutic options significantly impair treatment options in Africa. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective cohort at 1) Adama Hospital Medical College and 2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult HIV-infected patients presenting with suspected sepsis and assessed 28-day survival. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years and 61% being female. Overall, 11(13%) had positive CrAg tests, of which 5 had Cryptococcus detected in blood cultures. Despite high-dose fluconazole (1200mg/d) monotherapy in patients with positive CrAg tests, the 28-day mortality was 64%(7/11), being significantly higher than in CrAg-negative patients (9%(6/71); p&lt;0.001). Cryptococcosis is the leading cause of mortality among HIV-infected sepsis patients. CrAg screening in HIV-infected patients attending emergency department can minimize the cryptococcosis missing case irrespective of CD4 count and viral load. These findings warrant the need of a bundle approach for diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

Background and Objectives: HIV infection is a global public health problem that can lead to the progression of AIDS. Nutritional status and biochemical markers can significantly contribute to the progression of AIDS in HIV/AIDS patients. The main objective of this study is to examine the association between the nutritional and biochemical markers as well as BMI in HIV/AIDS patients in the kingdom of Bahrain. Methods: A retrospective cohort study, including 300 patients (248 males and 52 females) with HIV/AIDS in Bahrain. Various biochemical markers were collected from patients’ medical records including CD4^+ T cells counts, albumin, Hb, HCT, MCV, WBC, and creatinine. A semi-structured questionnaire using of a standardized food frequency questionnaire (FFQ) was used from which total energy and total macronutrients were calculate. Results: the mean BMI of participants was 27.20 kg/m2 with none of the participants had a BMI lower than 18.5 kg/m2 (underweight). The majority of patients’ dietary intake of macronutrients and total calories intake were either within or above the recommended RDA levels. The results also showed that all mean values of the nutritional and biochemical markers (CD4^+ T cells counts, albumin, Hb, HCT, MCV, WBC, and creatinine) are within the referenced normal ranges. A significant positive correlation of CD4^+ T cells counts, Hb, HCT and albumin at <0.05 level was found. There was no significant correlation between CD4^+ T cells counts and MCV, WBC and creatinine. A positive significant correlation was found between BMI, CD4^+ T cells counts, and WBC at <0.01 level. Conclusion: BMI values significantly correlated to biochemical markers of AIDS progression. Dietary pattern of participants was undiversified among participants, with high prevalence of obesity and overweight. Malnutrition among this study population was not present.

There is a significant overlap between HIV infection and substance use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in Methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV-latently infected U1 promonocytes with DA significantly increased viral p24 levels in the supernatant at 24 hrs, suggesting effects on activation and replication. Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase of p24 levels following DA stimulation. Conversely, DA increased the expression of these genes’ transcripts at the protein level, respectively MRP8 and MRP14, which form a complex also known as Calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding to the receptor for advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface and in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanistic for the delayed effect via DRD4 on p24 increase. To cross-validate MRP8/14 as a DA signature with biomarker value, we tested its expression in HIV+ Meth users’ brains and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in participants with detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may play a role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth.

The Centers for Disease Control and Prevention recommends everyone between 13-64 years be tested for HIV at least once as a routine procedure. HIV routine screening is reimbursable by Medicare, Medicaid, expanded Medicaid, and most commercial insurance plans. Yet, scaling-up HIV routine screening remains a challenge. We conducted a scoping review for studies on financial benefits and barriers associated with HIV screening in clinical settings in the U.S. to inform an evidence-based strategy to scale-up HIV routine screening. We searched Ovid MEDLINE®, Cochrane, and Scopus for studies published between 2006 - 2020 in English. The search identified 383 Citations; we screened 220 and excluded 163 (outside the time limit, irrelevant, or outside the U.S.). Of the 220 screened articles, we included 35 and disqualified 155 (did not meet the eligibility criteria). We organized eligible articles under two themes: financial benefits/barriers in healthcare settings (9 articles); and Cost-effectiveness in healthcare settings (26 articles). The review concluded recommendations in three areas: (1) Finance: Incentivize healthcare providers/systems for implementing HIV routine screening and/or separate its reimbursement from bundle payments; (2) Personnel: Encourage nurse-initiated HIV screening programs in primary care settings and educate providers on CDC recommendations; and (3) Approach: Use opt-out approach.

PrEP uptake in the Netherlands is growing but remains at suboptimal levels. Hence, the analysis of hurdles is paramount. Given the initial focus of PrEP provision among men-who-have-sex-with-men (MSM) via a demonstration project that was launched in June 2015, AmPrEP in Amsterdam, and pharmacies in the main urban areas (so called “Randstad”, entailing Amsterdam, Utrecht, Leiden, The Hague and Rotterdam), investigating regional differences is necessary. This study seeks to unravel regional differences jointly with psycho-social determinants of PrEP uptake. This cross-sectional study included 3,232 HIV-negative Dutch MSM recruited via the EMIS survey in late 2017. Prevalence and standardized prevalence ratio (SPR) of PrEP awareness, intention and uptake were measured on a regional level (Randstad vs. the rest of the country). Multilevel logistic modelling was conducted to identify the association of PrEP uptake with PrEP awareness and intention, sociodemographic, psycho-social determinants, and random effects from regional differences. MSM from the Randstad used more PrEP (SPR=1.4 vs. 0.7) compared to the rest of the country, but there were minor differences for awareness and intention. The regional distinction was estimated to explain 4.6% of the PrEP use variance. We observed a greater influence from PrEP intention (OR=4.5, 95%CI 2.0-10.1), while there was limited influence from the awareness of PrEP (OR=0.4, 95%CI 0.04-4.4). Lower education (OR=0.4, 95%CI 0.2-0.9) was negatively associated with PrEP uptake, however, no significant difference was found between middle and high education (OR=1.2, 95%CI 0.7-2.0). We showed that regional differences – MSM in non-urban regions – and other psycho-social determinants account for lower PrEP uptake. Based on these findings, more fine-tuned PrEP access with a focus on non-urban regions can be implemented, and tailored campaigns increasing intention/use can be conducted among target populations.

Background: Vertical transmission of HIV infection can occur during pregnancy, during childbirth or through breastfeeding. The recommendations issued by the various international guidelines (WHO 2010, EACS 2017, DHHS 2017) on the safety of breastfeeding of HIV-infected women in effective antiretroviral treatment do not provide univocal indications referring to individual countries the choice to advise or advise against such procedure. Methods: A retrospective study was conducted in a small cohort of HIV-infected pregnant women who, despite the information received, decided to breastfeed their children. The observation was carried out in the period between March 2017 and June 2021. In all newborns, prophylaxis therapy was initiated at birth, according to the treatment guidelines, the scheme adopted involved the administration of zidovudine (AZT) orally for 4 weeks, started immediately after the childbirth. Breastfeeding time was, on average, 5 months. Results: No contagion was diagnosed. All infants were tested for HIV-RNA at birth, 1, 3, and 6 months after birth, and 1, 3 and 3 months after stopping breastfeeding. Conclusions: The data obtained represent, in our opinion, a solicitation to discuss and re-evaluate scientific evidence that starting from "Undetectable Equals Untransmittable" (U = U) can open a scientific and cultural review of breastfeeding.

A mathematical model, composed of two non-linear differential equations that describe the population dynamics of CD4 T cells in the human immune system, as well as viral HIV particles, is proposed. The invariance region is determined, classical equilibria stability analysis is performed using the basic reproduction number, and numerical simulations are carried out, in order to illustrate stability results. Later, the model is modified with a delay term, which describes the time that cells require for immunological activation. This generates a two-dimensional integro-differential system, which is transformed into a system with three ordinary differential equations, via auxiliary variable use. For the new model, equilibrium points are determined, their local stability is examined, and results are studied by way of numerical simulation.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, has been declared by the World Health Organization (WHO) as a pandemic. Unfortunately, finding a vaccine or developing drugs from the scratch is a time-consuming luxury given the widespread and high fatality rates of the virus. In the short term, repurposing of drugs already in use seem to be the most rational step to quickly and effectively curb the virus. Several antiviral agents had been proposed as possible remedies, but the 4-aminoquinolines, Chloroquine (CHQ) and hydroxychloroquine (HCHQ) appear to be generating more interest. They are generic, cheaply available and have proven efficacy against malaria parasites in Africa. The human immunodeficiency virus (HIV), on the other hand, targets the immune system thereby reducing the patient’s ability to fight infections. Sadly, 68% of the global HIV burden occur in Africa. It is therefore anticipated that incidence of severe forms of COVID-19 could occur in Africa because of associated endemic conditions that compromise the immune system. With CHQ and HCHQ being considered for clinical use against COVID-19, there is a need to highlight their potential merits and confounding variables in the subgroup of patients with or without HIV.

Background: Trichomoniasis is the most common non-viral STI globally and yet is not a reportable disease. Trichomonas Vaginalis is an important source of reproductive morbidity and may increase risk of acquisition and transmission of HIV. WHO and CDC recommend various regimens of Nitro-Imidazoles for treatment. The common Nitro-Imidazoles used for Trichomoniasis are Metronidazole and Tinidazole, which vary in their cost, efficacy and side effect profile and it is relevant to study these factors, for better management of the patients. Objectives: This study aims to compare and study the efficacy, compliance of various treatment regimens, their outcomes and side-effects for Trichomoniasis, among STI clinic attendees in Trinidad. Methods: A clinical trial study was designed and after obtaining the informed consent a routine clinical examination was conducted and the swabs for Trichomoniasis tests were collected for diagnosis from the 692 participants. Out of 692 participants, Eighty two (82) patients with established diagnosis of Trichomonas infection were quasi-randomly treated using different regimens. Compliance to treatment, side effects and outcome were evaluated. Results: The prevalence of the Trichomoniasis in population attending our STI clinic is 11.9% and prevalence of HIV is 9%. Of the total 82 participants for the treatment, 80% were females; nearly 90% of the patients belonged to age group 15-45 years and over 60% were below 30 yrs. Among those diagnosed for Trichomonas vaginalis, 13.3% had associated HIV infection. The compliance with respect to single dose treatment was significantly better than the long duration oral regimen and has significant relation with side effects of the treatment. The outcome is generally better and comparable and shows no significant difference between different treatment regimens used in the study. Conclusions: Metronidazole and Tinidazole are commonly used drugs in various regimens. compliance is better with those treated with Tinidazole and Metronidazole stat, than with other groups. Outcome is comparable between these regimens, especially when combined with other important factors like abstinence and treatment of the partners. The treatment regimens mainly differ in the compliance and side effects profile, which suggests that to improve the compliance the drugs with less side effects, short course regimen would be a preferred choice.

HIV-1 assembly is a complex mechanism taking place at the plasma membrane of the host cell. It requires nice spatial and temporal coordination to end up with a full immature virus. Researchers have extensively studied HIV-1 assembly molecular mechanism during the past decades, in order to dissect the respective roles of viral proteins, viral genome and host cell factors. Nevertheless, the time course of the process has been observed in living cells only a decade ago. The very recent revolution of optical microscopy, combining high speed and high spatial resolution now permit to study assemblies and their consequences at the single molecule level within (living) cells. In this review, after a short description of these new approaches, we will show how HIV-1 assembly in cells has been revisited using these advanced super resolution microscopy techniques and how much it could make a bridge in studying assembly from the single molecule to the host cell.

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of Flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.

It is important to be able to detect and differentiate between distinct porcine enteric coronaviruses that can cause similar diseases. However, the existence of naturally occurring recombinant coronaviruses such as swine enteric coronavirus (SeCoV) can give misleading results with currently used diagnostic methods. Therefore, we have developed and validated three duplex real-time quantitative RT-PCR assays for the simultaneous detection of, and differentiation between, porcine epidemic diarrhea virus (PEDV) and SeCoV. Transmissible gastroenteritis virus (TGEV) is also detected by two out of these three assays. In addition, a novel triplex assay was set up that was able to detect and differentiate between these alphacoronaviruses and the porcine deltacoronavirus (PDCoV). The validated assays have low limits of detection, close to 100% efficiency and were able to correctly identify the presence of PEDV and SeCoV in 55 field samples, while 20 samples of other pathogens did not give a positive result. Implementing one or more of these multiplex assays into the routine diagnostic surveillance for PEDV will ensure that the presence of SeCoV, TGEV and PDCoV will not go unnoticed.

The induction of acoustic-mechanical oscillations to virus particles by illuminating them with microwave signals is analyzed theoretically. Assuming the virus particle being of spherical shape, its capsid consisting primarily of glycoproteins, a viscous fluid model is adopted while the outside medium of the sphere is taken to be ideal fluid. The electrical charge distribution of virus particle is assumed to be spherically symmetric with a variation along the radius. The generated acoustic-mechanical oscillations are computed by solving a boundary value problem analytically, making use of the Green’s function approach. Resonance conditions to achieve maximum energy transfer from microwave radiation to acoustic oscillation to the particle is investigated. Estimation of the feasibility of the technique to compete virus epidemics either for sterilization of spaces and/or use for future therapeutic applications is examined briefly.

Evolution remains an incessant process in viruses, allowing them to elude host immune response and induce severe diseases, impacting the diagnostic and vaccine effectiveness. Predicting emerging viral genomes is crucial, particularly in diseases like dengue, where viruses disrupt host cells, leading to fatal outcomes. Deep learning has been applied to predict dengue fever cases; there has been relatively less emphasis on its significance in forecasting emerging Dengue Virus (DENV) serotype. While Recurrent Neural Networks (RNN) were originally designed for modeling temporal sequences, our proposed DL-DVE generative and classification model, trained on complete genome data of DENV, transcends traditional approaches by learning semantic relationships between nucleotides in a continuous vector space instead of representing contextual meaning of nucleotide characters. Leveraging 2000 publicly available DENV complete genome sequences, our Long Short-Term Memory (LSTM) based generative and Feedforward Neural Network (FNN) based classification DL-DVE model showcases proficiency in learning intricate patterns and generating sequences for emerging serotype of DENV. The generative model showed accuracy of 93% and the classification model provided insight into the specific serotype label, corroborated by BLAST search verification. Evaluation metrics such as ROC-AUC value 0.818, accuracy, precision, recall and F1 score all to be around 99.00%, demonstrated the classification model’s reliability.  Our model classified the generated sequences as DENV-4, exhibiting 65.99% similarity to DENV-4 and around 63-65% similarity with other serotypes, indicating notable distinction from other serotypes. Moreover, the intra-serotype divergence of sequences with a minimum 90% similarity underscored their uniqueness. We analyzed the conserved motifs in the genome through MEME Suite (version 5.5.5). Our research strives to contribute to the ongoing fight against the Dengue virus by offering predictive insights into its genomic evolution. Looking ahead, proactive predictive modeling before mutations occur holds potential for guiding vaccine design and diagnostic kit development.

Medicinal plants are being tested as options to prevent infectious diseases in many countries. Baccharis crispa Spreng. (Asteraceae), is a native medicinal species widely used throughout South America. Our objective was to evaluate the antiviral activity of four wild populations of B. crispa from the province of Córdoba (Argentina) and determine if there is variability between them. The cytotoxicity of the extracts (chlorofom, ethanol and aquose) was evaluated by the neutral red uptake method. Using the plaque-forming unit reduction assay, virucidal and antiviral activity against Herpes Simplex type 1 and Chikungunya viruses were tested. Phytochemical screening of each extract was also performed. Puesto Pedernera (PP) population showed the best antiviral and virucidal effect, standing out the ethanolic extract as the least toxic and with the best inhibitory activity against both viral models. Villa del Parque (VP) population was inactive, regardless of the extract and the virus tested. The results revealed that extracts bioactivities vary significantly depending on the geographic area of collection, with PP and VP populations showing the most significant variability, not only in activity but also in chemical composition. These findings support the potential use of extracts as a source of therapeutic agents against different viruses.

Tilapia lake virus (TiLV) is the main tilapia-infecting virus worldwide, causing serious economic losses. However, there is no vaccine for this viral disease. Here, TiLV ORF10 (TiLV-ORF10) encoding a protein with abundant epitopes was constructed into the eukaryotic expression vector pcDNA3.1, and used to evaluate the immune protective effects in Nile tilapia (Oreochromis niloticus). RT-PCR and western blot analyses confirmed vaccine plasmid expression in tilapia muscle tissues. Moreover, the transcription levels of immunoglobulin M, toll-like receptor 2, myeloid differentiation factor 88, interleukin 8, tumor necrosis factor alpha, gamma-IFN, and nuclear factor κB immune-related genes were statistically significantly upregulated in the spleen, liver, and kidney of vaccinated tilapias (P < 0.05). TiLV challenge experiments showed that relative percent survival (RPS) was significantly enhanced in fish by this DNA vaccine. Moreover, RPS was enhanced further when using a higher amount of the DNA vaccine (85.72% RPS at a DNA dose of 45 μg pcDNA3.1–ORF10). Vaccination with pcDNA3.1–ORF10 significantly reduced virus replication, as evidenced by the low amount of virus in the spleen, liver, and kidney of vaccinated tilapias after TiLV challenge. Thus, pcDNA3.1–ORF10 could induce protective immunity in tilapia and may be a potential vaccine candidate for controlling diseases caused by TiLV.

Arthropod-borne viruses belonging to the flavivirus genus possess an enormous relevance in public health. Neotropical non-human primates (NPs) have been proposed to be infected more frequently with flaviviruses due to their arboreal and diurnal habits, their genetic similarity to humans and their relative closeness to humans. However, the only known flavivirus in America that is maintained by sylvatic cycles involving NPs is Yellow Fever virus (YFV), and the NPs role as potential hosts of flaviviruses is still unknown. Here, we examined flavivirus exposure in 86 free range and captive NPs of Costa Rica to evaluate their involvement in flavivirus transmission cycles and their potential as flavivirus hosts. We used a highly-specific micro plaque reduction neutralization test (micro-PRNT) to determine the presence of antibodies against YFV, Dengue virus 1-4 (DENV), Zika virus, West Nile Virus (WNV) and Saint Louis Encephalitis virus (SLEV). We found evidence of seropositive NPs to DENV-1 8.2% (homotypic –3/86, heterotypic – 4/86), SLEV 15.1% (homotypic – 10/86, heterotypic – 2/86), WNV 2.3% (homotypic – 2/86) and 8.1% (7/86) undetermined Flavivirus species. No antibodies against YFV or ZIKV were found. This work provides compelling serological evidence of exposure in NPs of flaviviruses associated with urban cycles, i.e. DENV, and confirms decades of circulation of SLEV in the same environments. Also, the range of years of sampling and the socioeconomic region was statistically significant for the presence of Dengue and Flavivirus undetermined seropositive individuals, respectively. Both the years and socioeconomic regions with greater seroprevalence coincide with the years and socioeconomic regions with high numbers of Dengue human cases for the country. Our work suggests bidirectional? circulation of different flaviviruses between humans and wildlife with public health importance and underscores the necessity of further surveillance for flaviviruses in the humans/wildlife interface in Central America.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (&gt;200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p&lt;.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

A striking aspect of COVID-19 is the difference in the outcome of the infection between different countries, and different ethnic groups within one country. We surveyed the literature on SARS-CoV-2 complemented with comparative publications on SARS-CoV and other coronaviruses to capture the current understanding of virus – host interactions including virus subtypes, transmission, zoonotic aspects, and potential host determinants.

Visceral leishmaniasis (VL) results from infection by the protozoa Leishmania infantum and L. donovani. HIV-coinfected patients may have a relapsing course of VL, even after secondary prophylaxis with amphotericin B. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both patients in the first episode and with relapsing VL. Still, the strongest blood cell associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and 23 with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low, low-density lipoprotein. After CD4+ decrease, lymphocyte CD8+ reduction seem to be the final stage of the immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia provoked by the co-occurrence of both diseases, which can finally lead to death.

Two decades after the antiretroviral therapy (ART) introduction, several challenges still prevail in maintaining people living with HIV (PLHIV), even with "Test and Treat" and/or "Rapid Start of ART" initiatives, as well as the scale-up of ART worldwide to promote access and adherence to treatment. This review examined articles on ART adherence in Africa between 2016 and 2023, published in English and indexed in PubMed. A total of 16 articles out of 2415 were eligible and included for analyses. Overall, ART adherence rates in SSA regions ranged from 43% to 84%. Rates in the centre of the SSA region ranged from 58% to 80%, in the north from 50% to 83%, in the south from 77% to 84%, in the west from 43% to 60% and in the east from 69% to 73%. Most African countries use the self-report to assess treatment adherence, although unreliable. The main factors with negative influence on ART adherence were comorbidities, lack of motivation, socioeconomic difficulties or side effects. Conclusion: Adherence to ART is a good indicator for controlling the spread of HIV. It is important to overcome the barriers that make it difficult to comply with ART and reinforce the factors that facilitate the accession of medication.

The metabolome is the composition of all molecules present in an organism, metabolomics science allows us to qualitatively and quantitatively analyze metabolites and understand the biochemical state in response to genetic and environmental changes. The purpose of the study was to identify the metabolomic profile of biofluids (saliva and urine) of patients living with HIV/AIDS (PLHIV/AIDS), and establish a possible association of metabolites with periodontal disease (PD). It was an analytical and descriptive study composed of 65 patients seen at the Center for Studies and Care for Special Patients (CEAPE-UNIP), who were divided into 4 predetermined groups (G), G1-PLHIV/AIDS and without PD, G2- PLHIV/Aids and with PD, G3-people without HIV/Aids and without PD, G4-people without HIV/Aids and with PD. The results showed that in relation to urine, G2 has the highest mean area of concentration of metabolites. There are statistically significant differences between G1 and G2. The area of G2 is greater than G3, and greater than G4. There are no differences between G3 and G4, neither between G1 and G3, nor between G1 and G4. Regarding saliva, there are no statistically significant differences when comparing the groups for the mean areas of concentration of metabolites. We conclude that it was possible to distinguish the metabolic profile of PLHIV/Aids with periodontal disease and without periodontal disease, some metabolites are over expressed in PLHIV/Aids and with PD. Most of the metabolites of the carbohydrate group are under expressed in PLHIV/AIDS, even in systemic compensation situations these patients presented a different metabolic profile.

Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is relatively prevalent. In alignment with this, HCV co-infection is associated with an increased size of the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it is crucial to comprehend the physiological mechanisms governing the latency and reactivation of HIV in reservoirs. Consequently, our study delves into the interplay between HCV/HIV coinfection in liver cells and its impact on the modulation of HIV latency. We utilized the latently infected monocytic cell line (U1) and the latently infected T cell line (J-Lat) and found that mediators produced by the infection of hepatic stellate cells and hepatocytes with HIV and HCV, respectively, were incapable of inducing latency reversal under the studied conditions. This may favor the maintenance of the HIV reservoir size among latently infected mononuclear cells in the liver. Further investigations are essential to elucidate the role of the interaction between liver cells in regulating HIV latency and/or reactivation, providing a physiologically relevant model for comprehending reservoir microenvironments in vivo.

Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell, in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi, and tumors. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic center of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

HIV diagnosis and poor HIV management have various detrimental impacts on the lives of people living with HIV (PLHIV). As part of a large qualitative study investigating HIV risk factors and impacts, with the suicide topic not being a focus, this paper describes factors contributing to suicidal ideation and attempts that arose naturally in the stories of women living with HIV (WLHIV) in Yogyakarta and Belu districts, Indonesia. The participants were recruited using the snowball sampling technique. Guided by a qualitative data analysis framework, the data were thematically analysed. Findings indicated participants experienced immense psychological challenges due to the infection, spousal transmission, fear of mother-to-child transmission, and losing a child due to AIDS, which triggered suicidal ideation and attempts. The women’s lack of awareness of HIV management strategies resulted in them feeling trapped and overwhelmed. Associated negative thoughts and the anticipation and experience of stigma relating to their HIV status were influencing factors for thoughts of suicide among participants. Lack of social support from family and friends during the early stage of HIV diagnosis, compounded with pre-existing financial difficulties, lack of income, unemployment, and feeling overburdened, also triggered the women’s thoughts of suicide. Other influencing factors for suicidal ideation and attempts among the women were family breakdown following HIV diagnosis and this was reflected in family disputes, husband-wife separation or divorce, mother-child separation by other family members, reported concern about future relationships, and fear of being rejected or abandoned by their partner due to their HIV positive status. The findings indicate the need for a nuanced approach to counselling within HIV care interventions for couples to support the acceptance of each other’s HIV status whilst maintaining psychological wellbeing. Additionally, the findings indicate the importance of HIV education and awareness among community members for the de-stigmatisation of HIV and to increase the acceptance of PLHIV within families and communities.

I. Introduction: Adherence to ART reduces morbidity and mortality among PLHIV by suppression of viral replication, restoration and preservation of immune function. However, poor adherence may lead to treatment failure and death. PLHIV have high probability of treatment interruptions due to lockdowns related to COVID-19 protocol. Mortality rate is higher among COVID-19 patients with HIV than those with COVID-19 only. This led to determination of the barriers to antiretroviral medication adherence in PLHIV at the time of COVID-19 pandemic and seek significant association between identified HIV treatment barriers and socio-demographic characteristics. II. Methods: A cross-sectional study using online survey questionnaire was distributed via social media. Sample size was computed using Open Epi software. Data was analyzed using Stata software. Categorical variables and quantitative data were summarized using frequencies and percentages, and mean and standard deviation respectively. Chi-square test or Fisher’s exact test, whichever is more appropriate, was used to determine association between socio-demographic characteristics and HIV treatment barriers. III. Results: There is a total of 116 respondents, 115 were males, homosexual (59.5%), with mean age of 30.25 years old (SD = 6.22) and majority (53.4%) were from NCR. The most common HIV treatment barriers reported by PLHIV in accessing treatment and care were unavailability of transportation and cost of courier services for ARV delivery (62.1%), location of treatment hubs (52.6%) and financial assistance (37.9%). IV. Conclusion: There is significant association between location of treatment hubs and respondents who finished college/graduate studies; checkpoints and crossing borders and: 1. respondents from Northern Luzon, 2. unemployment; financial assistance and: 1. Respondents 18 to 25 years old, 2. unemployment, 3. respondents who finished elementary/high school; psychosocial support and: 1. Respondents from NCR, 2. Respondents 26 to 30 years old;

Africa is expected to have a lion’s Share in the world’s population growth by 2050. At the same time, the World Health Organisation (WHO) reported that roughly 3.4 percent (1/25) of African adults live with HIV making the contient the most severely affected by the HIV pandemic. Consequently, this study, the first of its kind, investigates the impact of population growth and HIV incidence on economic growth and economic development in Africa by utilizing the Pooled Mean Group (PMG) estimator on data from 1990 to 2020 across 29 countries. The results show that population growth has a postive long run impact on Gross Domestic Product (GDP) but has a negative long run impact on per capita GDP, albeit the effects are insignificant in the short run. The incidence of HIV has a negative long run impact on both GDP and per capita GDP although its effect is not significant in the short run. The study, therefore, calls for the advancement of family planning practices and the usage of contraceptives to simultaneously control population growth and curb the spread of HIV incidence. The study futher calls for African governments to increase budgetary allocations to the health and education sectors, as these policy perspectives have the potential of increasing the human capital stock and at the same time enhancing the health status of the work force for sustained growth and development.

Despite intensive HIV education and prevention efforts in the past years, stigmatizing attitudes toward people living with HIV (PLWH) remain a major barrier to HIV prevention and treatment efforts in Vietnam. The purpose of this study was to examine the prevalence of stigmatizing attitudes regarding HIV and identifying correlative factors that impact perceptions of PLWH among women migrant workers working in the industrial zones (IZ) in Hanoi, Vietnam. A cross-sectional study was conducted among 1061 women migrant workers aged 18 to 29 from January to November 2020 in Hanoi, Vietnam. Stigmatizing attitudes toward PLWH were measured using a four-item scale. Multiple logistic regression was conducted to examine factors associated with stigmatizing attitudes. Over seventy-six (76.2 %) of the participants reported having at least one of the four stigmatizing attitudes. Greater levels of stigmatizing attitudes toward PLH were significantly associated with lower HIV knowledge, lower education and being Kinh (the ethnic majority in Vietnam). A high level of stigmatizing attitudes toward PWH among the study participants suggests that there is an urgent need for the development of appropriate culturally interventions and outreach education activities to reduce stigmatizing attitudes toward PWH among women migrant workers working in the IZs in Vietnam.Despite intensive HIV education and prevention efforts in the past years, stigmatizing attitudes toward people living with HIV (PLWH) remain a major barrier to HIV prevention and treatment efforts in Vietnam. The purpose of this study was to examine the prevalence of stigmatizing attitudes regarding HIV and identifying correlative factors that impact perceptions of PLWH among women migrant workers working in the industrial zones (IZ) in Hanoi, Vietnam. A cross-sectional study was conducted among 1061 women migrant workers aged 18 to 29 from January to November 2020 in Hanoi, Vietnam. Stigmatizing attitudes toward PLWH were measured using a four-item scale. Multiple logistic regression was conducted to examine factors associated with stigmatizing attitudes. Over seventy-six (76.2 %) of the participants reported having at least one of the four stigmatizing attitudes. Greater levels of stigmatizing attitudes toward PLH were significantly associated with lower HIV knowledge, lower education and being Kinh (the ethnic majority in Vietnam). A high level of stigmatizing attitudes toward PWH among the study participants suggests that there is an urgent need for the development of appropriate culturally interventions and outreach education activities to reduce stigmatizing attitudes toward PWH among women migrant workers working in the IZs in Vietnam.

In addition to CD4+ T lymphocytes, myeloid cells, and, particularly, differentiated macrophages, are targets of the human immunodeficiency virus type-1 (HIV-1) infection via interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication although with substantial differences. In contrast to activated CD4+ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing of curtailing virus replication in macrophages and T cells particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factor determining restriction or reactivation of virus replication in myeloid cells.

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. In this respect the identification of single agents with multitarget potential might represent the ideal solution. Accordingly, a small library of biphenylhydrazo 4-arylthiazoles derivatives has been synthesised and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity.

The outbreak of novel coronavirus (COVID-19) infections in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking to repurpose HIV protease inhibitors and nucleoside analogues for COVID-19, with evaluations based on docking scores calculated by AutoDock Vina and RosettaCommons. Our results suggest that Indinavir and Remdesivir possess the best docking scores, and comparison of the docking sites of the two drugs reveal a near perfect dock in the overlapping region of the protein pockets. After further investigation of the functional regions inferred from the proteins of SARS coronavirus, we discovered that Indinavir does not dock on any active sites of the protease, which may give rise to concern in regards to the efficacy of Indinavir. On the other hand, the docking site of Remdesivir is not compatible with any known functional regions, including template binding motifs, polymerization motifs and nucleoside triphosphate (NTP) binding motifs. However, when we tested the active form (CHEMBL2016761) of Remdesivir, the docking site revealed a perfect dock in the overlapping region of the NTP binding motif. This result suggests that Remdesivir could be a potential therapeutic agent. Clinical trials still must be done in order to confirm the curative effect of these drugs.

This paper describes new horizons in the diversity and taxonomy of negev-like viruses encoding the membrane-embedded SP24 protein. First, our data extend the known host range of SP24-encoding negev-like viruses to include brown algae, fungi, green plants, the phylum Entoprocta, the phylum Mollusca, and vertebrates. Second, our phylogenetic analysis suggests that the evolution of the SP24 gene family may have involved frequent events of inter-order virus genome shuffling. Third, the identification of 2-3 copies of SP24 protein genes in some virus RNAs shows that virus genomes may have acquired additional SP24 genes during the evolutionary process due to duplications or new acquisition steps. Forth, the broad host specificity of some SP24-encoded viruses may be related to an important adaptive role of SP24. Fifth, insect and nematode genomes may acquire viral SP24 genes by putative horizontal transfer from negev-like viruses known to infect species of both taxa.

Infection with Ebola virus (EBOV) is responsible for haemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluc-based protein complementation assay (NPCA) and isolated two compounds disrupting the interaction of the EBOV protein fragment VP35IID with the N terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, we support further testing of the compounds in other species, as well as against further negative sense RNA viruses.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

Background: Every year, millions of people are hospitalized, and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection, and thus contribute to morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds of medicines commonly prescribed in Central Norway. Then we constructed a drug-target interaction network and identified potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on viability, transcription and metabolism of mock- and A/WSN/33(H1N1)-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that many drugs, such as acetylsalicylic acid, atorvastatin, candesartan, and hydroxocobalam, could target and modulate FLUAV-host cell interaction. In vitro experiments showed that these and other compounds at non-cytotoxic concentrations differently affected transcription and metabolism of mock- and FLUAV-infected cells. Conclusion: Many commonly prescribed drugs modulate FLUAV-host cell interactions in vitro and therefore could affect their interplay in vivo, thus, contributing to morbidity and mortality of patients with influenza virus infections.

It remains poorly understood how the life history strategies and transmission ecologies of viruses of plants, arthropods, and vertebrates are interrelated. The present analysis hinges on the virus transmission success. Virus transmission reflects where in the host-body viruses are retained or replicating. Plants, arthropods, and vertebrates share a protective outer-layer, a circulatory system, and reproductive organs. The latter enables vertical virus transmission and associates with virus-host mutualism. Two broadly opposing virus life history strategies are considered. Acute viruses tend to be replicative and are swiftly transmitted to the next host. Instead, persistent viruses keep virus replicating costs and host damage to a minimum. The intertwined life histories and transmission ecologies are accordingly pieced together, based on the virus mono- or instead dual-host tropism, the location of virus retention or replication on or in the host-body, the presence of cyclical or mechanical transmission by arthropods, and of horizontal and vertical host-to-host transmission modes. It is shown that in the arthropod and in the vertebrate animal host, virus circulation in the hemocoel or blood circulation goes hand-in-hand with vertical transmission. Instead, plant phloem viruses do not transmit via seed. The latter is the rule for the plant-only viruses. The risk management implications are discussed in brief.

The success of many viruses depends upon cooperative interactions between viral genomes. For example, viruses that coinfect the same cell can share essential gene products, such as replicase, the enzyme that replicates the viral genome. However, when cooperation occurs, there is the potential for ‘cheats’ to exploit that cooperation. We suggest that: (1) the biology of viruses makes viral cooperation particularly susceptible to cheating; (2) cheats are common across a wide range of viruses, including viral entities that are already well studied, such as defective interfering genomes, and satellite viruses. Consequently, evolutionary theory developed to explain cheating offers a conceptual framework for understanding and manipulating viral dynamics. At the same time, viruses offer unique opportunities to study how cheats evolve, because cheating is relatively common in viruses, compared with taxa where cooperation is more usually studied, such as animals.

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages, and presents a novel efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses: from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. Best practice and also rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of the multivalent soft-matter nanorods.

Novel segmented tick-borne RNA viruses belonging to the group of Jingmenviruses (JMVs) are widespread across Africa, Asia, Europe, and America. In this work, we obtained whole-genome sequences of two Kindia tick virus (KITV) isolates and performed modeling and functional annotation of the secondary structure of 5’ and 3’ UTRs from JMV and KITV viruses. UTRs of various KITV segments are characterized by: (1) polyadenylated 3’ UTRs; (2) 5’ DAR and 3’ DAR motifs; (3) a highly conserved 5’-CACAG-3’ pentanucleotide; (4) a La protein binding site; (5) multiple UAG sites providing interactions with the MSI1 protein; (6) three homologous sequences in the 5’ UTR and 3’ UTR of segment 2; (7) the segment 2 3’ UTR of a KITV/2017/1 isolate comprises two consecutive 40 nucleotide repeats forming a Y-3 structure; (8) a 35-nucleotide deletion in the second repeat of the segment 2 3’ UTR of KITV/2018/1 and KITV/2018/2 isolates, leading to a modification of the Y-3 structure; (9) two pseudoknots in the segment 2 3’ UTR; (10) the 5’ UTR and 3’ UTR are represented by patterns of conserved motifs; (11) the 5’-CAAGUG-3’ sequence occurs in early UTR hairpins. Thus, we identified regulatory elements in the UTRs of KITV, which are characteristic of orthoflaviviruses. This suggests their functional significance for the replication of JMVs and the evolutionary similarity between orthoflaviviruses and segmented flavi-like viruses.

Invasive weeds cause significant crop yield and economic losses in agriculture. The highest in-direct impact may be attributed to the role of invasive weeds as virus reservoirs especially within the commercial growing areas. The new tobamovirus tomato brown rugose fruit virus (ToBRFV), recently identified in the Middle-East, overcomes the Tm-22 resistance allele in the cultivated tomato varieties grown in greenhouses. In this study, we determined the role of invasive weed species as potential hosts for ToBRFV and pepino mosaic virus (PepMV). Out of all tested weed species, the invasive species So-lanum elaeagnifolium and S. rostratum, mechanically inoculated with ToBRFV, were positive for To-BRFV in both enzyme linked immunosorbent assay (ELISA) and RT-PCR tests. S. rostratum was also positive for PepMV. No conspicuous phenotype was observed on ToBRFV infected S. elaeagnifolium plants suggesting a hostplant associated defense response. S. rostratum plants inoculated with either ToBRFV alone or a mixture of ToBRFV and PepMV-IL, contained high ToBRFV levels. In addition, when inoculated with ToBRFV or PepMV-IL disease symptom manifestations were observed in S. rostratum plants and the symptoms were exacerbated upon mixed infections with both viruses. The distribution and abundance of both Solanaceae species increase the risks of virus transmission between species.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Canine distemper virus (CDV) is a serious contagious disease of canines, cats and sometimes ra-coons. The study included seven raccoons from Timisoara Zoo. The detection of CDV in all raccoons was accomplished using qRT-PCR, but several other exams were also conducted. Clinically, severe digestive disorders were observed, characterized by diarrhea and repeated hematemesis. Pseudomembranous gastroenteritis, congestion and pulmonary edema were found during the ne-cropsy of two racoons. Immunohistochemically, the brown color was highlighted in the examined sectionsand it was present in the cytoplasm of the cells from the germinal centers of the medullary area. Histopathological examination revealed lymphocyte depletion and intranuclear and intracy-toplasmic inclusions in the intestine. Based on the qRT-PCR assay, laboratory tests and lesions ob-served, it was established that the raccoons got infected with CDV, and two of them died as a result. The necropsy, histological lesions and immunohistochemical results are comparable between dogs and racoons. Through the results obtained, it was concluded that the interspecific infection is possible and the epidemiological risk of infection transmitted by racoons to domestic animals, such as dogs and cats, needs to be examined in the future.

"Medusaviridae" is a proposed family of large DNA viruses so far represented by a sole virus isolated from a hot spring. In the present study, we report the isolation and genome sequencing of a new member of this family, medusavirus stheno, discovered from a freshwater sample with Acanthamoeba castellanii coculture.

BK polyomavirus (BKPyV) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein do not propagate to wild-type levels and fail to release from host cells. Despite this, loss of agnoprotein does not impair virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.

The recently discovered Jingmenvirus group includes viruses with a segmented genome, RNA of a positive polarity, and several proteins with distant homology to the proteins of the members of the genus Flavivirus. Some Jingmenvirus group members, namely Alongshan virus (ALSV) and Jingmen tick virus, are reported to be tick-borne human pathogens, causing a wide variety of symptoms. ALSV is widely distributed in Eurasia, yet there is no reliable assay for its detection. Here, we describe a qPCR system for the detection of ALSV. Our data show that this system can detect as low as 10⁴ copies of ALSV in the probe. It shows no amplification with common tick-borne viruses circulating in Eurasia, Yanggou tick virus—another member of the Jingmenvirus group—or some known members of the genus Flavivirus. The qPCR system was tested have no non-specific signal for Ixodes ricinus, I. persulcatus, Dermacentor reticulatus, D. marginatus, Haemaphysalis concinna, and H. japonica ticks. Overall, the qPCR system described here can be used for reliable and quantitative ALSV detection.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The development of compartmentalized neuron culture systems has been invaluable in the study of neuroinvasive viruses, including the alpha herpesviruses Herpes Simplex Virus 1 (HSV-1) and Pseudorabies Virus (PRV). This chapter provides updated protocols for assembling and culturing rodent embryonic superior cervical ganglion (SCG) and dorsal root ganglion (DRG) neurons in Campenot trichamber cultures. In addition, we provide several illustrative examples of the types of experiments that are enabled by Campenot cultures: 1. Using fluorescence microscopy to investigate axonal outgrowth/extension through the chambers, and alpha herpesvirus infection, intracellular trafficking, and cell-cell spread via axons. 2. Using correlative fluorescence microscopy and cryo electron tomography to investigate the ultrastructure of virus particles trafficking in axons.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Introduction: It is widely recognized that young female sex workers (YFSWs) are at greater risk of HIV infection than their older counterparts. This study aims to unravel the complexities surrounding HIV transmission among this demographic group, by determining the prevalence of HIV infection and identifying high-risk sexual practices associated with HIV infection among YFSWs in Lubumbashi, in the Democratic Republic of the Congo. Methods: We conducted an analytical cross-sectional study and used a comprehensive sample of all YFSWs who presented to the HIV/Sexually Transmitted Infections Screening and Treatment Center in Lubumbashi between April 2016 and December 2017. We collected data on age, number of years in the practice of selling sex, number of sexual encounters per day, number of clients per week, systematic condom use, having suffered from sexually transmitted infections in the last 3 months before the survey, regular alcohol consumption, having anal sex in the last 12 months, having had forced sex in the last 12 months. Multiple logistic regression was used to identify potential factors associated with HIV infection. Results: A total of 572 YFSWs were included in the study, 19 of whom were HIV-positive (3.3%; 95% CI: 2.1% - 5.1%). Participants who were forced to have sex (adjusted OR=12.2; 95% CI: 3.2 - 46.4; p&lt;0.0001), those who did not use condoms systematically (adjusted OR=4.1; 95% CI: 1.3 - 13.0; p=0.018), and those who had anal sex (adjusted OR=23.8; 95% CI: 6.9 - 82.4; p&lt;0.0001) were more likely to be HIV-positive. Conclusion: The results of this study suggest that HIV prevalence among YFSW is higher than in the general Congolese population, and is significantly associated with high-risk sexual practices. Interventions aimed at increasing YFSW’s knowledge of high-risk behaviors should be vigorously pursued.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combat the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

Background: Currently, a Dolutegravir (DTG)-based regimen is administered to women on option B plus to prevent mother-to-child transmission (MTCT) of the virus. However, its effect on reducing MTCT of human immunodeficiency virus (HIV) among exposed infants over the previously used Efavirenz (EFV)-based regimen is unknown. Objective: This study aimed to compare the effects of DTG-based and EFV-based regimens on the MTCT of HIV among exposed infants in southern Ethiopia. Methods: A retrospective before-after study design was employed from March to May 2023 among 958 mother-infant pairs (479 on EFV-based and 479 on DTG-based regimens) enrolled in the prevent mother-to-child transmission (PMTCT) care from September 2015 to February 2023. The outcome variable was the HIV infection status among the exposed infants. A log-binomial model was employed and the proportion was computed to compare the incidence of MTCT of HIV in both groups. The risk ratio (RR) with 95% confidence interval (CI) was calculated to assess the predictor variables. Results: Mothers on a DTG-based regimen were approximately 44% (adjusted risk ratio (aRR): 0.56; 95% CI: 0.44, 0.70) less likely to transmit HIV to their infants than those on an EFV-based regimen. In addition, poor/fair adherence to antiretroviral therapy (ART) (aRR: 5.82; 95% CI: 3.41, 9.93), home delivery (aRR: 3.61; 95% CI: 2.32, 5.62), mixed feeding practice (aRR: 1.83; 95% CI: 1.45, 2.3), and not receiving antiretroviral prophylaxis (aRR: 3.26; 95% CI: 1.6, 6.64) were found to increase the risk of MTCT of HIV infection, whereas older maternal age (aRR: 0.93; 95% CI: 0.9, 0.96) was a protective factor.Conclusion: The Dolutegravir-based regimen significantly reduced MTCT of HIV among exposed infants compared to the EFV-based regimen. Thus, DTG-based first-line ART regimen supplementation should be sustained to achieve global and national targets for zero new infections in HIV-exposed infants.

In this review article will be described the (wide) variety of approaches that I envisaged to develop a specific therapy of viral infections: (i) interferon and its inducers, (ii) HSV, VZV and CMV inhibitors, (iii) NRTIs (nucleoside reverse transcriptase inhibitors), NtRTIs (nucleotide reverse transcriptase inhibitors) and NNRTIs (non-nucleoside reverse transcriptase inhibitors) as HIV inhibitors, (iv) NtRTIs as HBV inhibitors and finally, (v) the transition of an HIV inhibitor to a stem cell mobilizer, as exemplified by AMD-3100 (Mozobil®).

Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels, viral eradication has not been achieved due to HIV-1 persistence in resting CD4+ T-cells. We, therefore, characterized the tat gene, which is essential for HIV-1 replication, from 20 viro-logically controlled HIV-infected (HIV+) older patients on long-term ART with improved CD4+ T-cell counts. PBMC genomic DNA from HIV+ patients were used to amplify tat gene by PCR fol-lowed by nucleotide sequencing and analysis. Phylogenetic analysis showed that each patient’s tat sequences were confined to their own subtrees and well discriminated from other patients’ sequences. Moreover, there was a low degree of viral heterogeneity and lower estimates of genetic diversity within these patients’ tat sequences. Most patients’ Tat deduced amino acid sequences showed intact open reading frames and maintained the important functional domains for Tat functions, including transactivation, TAR binding and nuclear localization. Furthermore, Tat deduced amino acid sequences showed variation in previously characterized cytotoxic T lym-phocytes (CTL) epitopes, suggesting escape mutants. In conclusion, a low degree of genetic varia-bility and conservation of functional domains and variations in CTL epitopes were the features of tat sequences from 20 HIV+ older patients with undetectable viral load on long-term ART.

HIV-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWH) who naturally control HIV-1 replication. The ability of HICs to control the expression of endogenous retroviruses has not been previously addressed. In this study, we measured ERVK-6 RNA expression in PBMCs of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 restriction factors. Our study reveals that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with both ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1. In our previous study, these two cellular restriction factors were upregulated in HICs compared with control groups. Interestingly, p21 and MCPIP1 limit the activation of macrophages and T cells by downregulating the activity of NF-kB, a transcription factor that stimulates the LTR-driven transcription of HIV-1 and HERV-K proviruses. These findings support that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both HIV-1 and endogenous retroviruses.

To assess the impact of tourism on the incidence of HIV and AIDS using Malaysian epidemiological data over the period of 1986-2011 with additional consideration for newborns infected with HIV. A population-level mathematical model was used to investigate: i) the role of tourism in the spread of HIV and measures used to reduce HIV spread in Malaysia; ii) whether the stability of infectious disease transmission is dependent on the flow of visiting tourists. We first derived an equation for the reproduction number (R0) threshold to quantify the contagiousness of HIV in Malaysia. Sensitivity analyses were used to determine the effect of various parameters on HIV transmission with respect to the increase in tourism. Our findings suggest that a stable disease-free state is sustainable based on the low value of R0 was 0.0017. This result is encouraging from a public health perspective. Approximately 14% of outbound tourists who leave the country return infected with HIV and the difference between the rate at which tourists move to the susceptible category and the rate at which tourists leave the susceptible is category is 12%. Estimated parameters for the influx of tourist rates, δ=1.1540x10-3[1.1477x10-3 - 1.15954x10-3], δ1=7.7901x10-4[7.7867x10-4 - 7.79418x10-4], and δ2=1.4030x10-8[-7.2287x10-7-7.5096x10-7], significantly impacted the spread of HIV in Malaysia. Some significant adjustments were made to the expected parameters. The methods used are helpful to public health analyses and provide a framework for epidemiological modeling of HIV spread among tourists. The trend and magnitude of tourist inflows may be determinants in the incidence of HIV and AIDS in Malaysia.

In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU including identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-Transgenic (HIV-Tg) animal model, to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone (oxy). RNA-Seq analysis on the striatum - a brain region that is primarily targeted by both HIV and drugs of abuse - identified key differentially expressed markers post-METH and oxy exposure. Furthermore, ClueGO analysis and Ingenuity Pathway Analysis (IPA) revealed crucial molecular and biological functions associated with ATP-activated adenosine receptor, neuropeptide hormone activity, and the oxytocin signaling pathway to be altered between the different treatment groups. The current study further reveals the harmful effects of chronic PSU and HIV infection that can subsequently impact neurological outcomes in polysubstance users with HAND.

The Virus HIV-1 infection still represents a serious disease even if actually it is transformed in chronic pathology. Considering the crucial role of the enzyme Protease in life cycle of HIV many efforts have been made in the research of new organic compounds showing inhibitory activity. After development of several series of non peptidic inhibitors we report here the synthesis of novel simple HIV-Protease inhibitors containing heteroaryl carboxamides and their antiviral activity in vitro and in HEK293 cells. Benzofuryl- benzothienyl- and indolyl rings as well as aryl sulfonamides with different electronic properties have been introduced by efficient synthetic procedures. All compounds showed inhibitory activity similar to the commercial drug Darunavir, effective against both wild-type HIV-1 protease and that containing the V32I or V82A mutations. ADME properties were also evaluated, showing the potential of such compounds to be developed as drugs.

PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. The major interaction site is formed by the unusually long complementarity determining region (CDR) H3. The CDRH3 residue Tyr100H is known to represent a tyrosine sulfation site; however, this modification is not present in the experimental complex structure of PG16 with full-length HIV-1 Env. To investigate the role of sulfation for this complex, we modeled the sulfation of Tyr100H and compared the dynamics and energetics of the modified and unmodified complex by atomistic molecular dynamics simulations. Our results show that sulfation does not affect the overall conformation of CDRH3, but still enhances gp120 interactions both at the site of mutation and for the neighboring residues. This stabilization affects not only protein-protein contacts, but also the interactions between PG16 and the gp120 glycan shield. Further, we also investigated whether PG16-CDRH3 is a suitable template for the development of peptide mimetics. For a peptide spanning residues 93-105 of PG16 we obtained an experimental EC50 value of 3nM for the binding of gp120 to the peptide. This affinity can be enhanced by almost one order of magnitude by artificial disulfide bonding between residues 99 and 100F. In contrast, any truncation results in significantly lower affinity, suggesting that the entire peptide segment is involved in gp120 recognition. Their high affinity makes PG16-derived peptides useful building blocks for further optimization to obtain a potent inhibitor that efficiently blocks HIV-1 infection.

Background: Histoplasmosis is a systemic mycosis, present globally. We aimed to describe cases of histoplasmosis (Hc) and to establish a risk profile associated to Hc in HIV-infected patients (HIV+). Methods: This was a retrospective study of patients with a clinical-. laboratorial diagnosis of Hc. Data was fed into REDCap and statistical analysis was done with R . Results: We included 99 records, 65 HIV+ and 34 HIV-. Average age was 39 years. Median time from onset to diagnosis was 8 weeks in HIV- and 22 weeks in HIV+. Disseminated histoplasmosis occurred in 79.4% HIV+, vs 36.4% HIV-. Median CD4 count was 70. Co-infection with tuberculosis was present in 20% of HIV+. Blood cultures were positive in 32.3% of HIV+ vs 11.8% of HIV- (p=0.025); bone marrow culture was positive in 36.9% vs 8.8%(p=0.003). Most HIV+ patients (71.4%) were hospitalized. On univariate analysis, anemia, leukopenia, intensive care, use of vasopressors and mechanical ventilation were associated with death in HIV+. Conclusions: Most of our patients with histoplasmosis were HIV+, presenting advanced AIDS. Diagnosis was late in HIV+ patients, and they frequently presented disseminated Hc, required hospitalization, and died. Early screening for Hc in HIV+ and drug induced immunosuppressed patients is crucial.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

HIV-associated neurocognitive disorder (HAND) is an array of neurocognitive changes associated with HIV infection, and the roles of microRNAs in HAND are not completely revealed yet. Based on published data and publicly available databases, we constructed an integrated miRNA-mRNA network involved in HAND. Bioinformatics analyses, including gene ontology, network analysis, and KEGG pathway analysis, were applied for further study of the network and the genes of the network. The axon guidance KEGG pathway, three genes NTNG1, EFNB2, CXCL12, and 17 miRNAs which regulates them, are spotlighted in our study. This study provides new perspectives to the knowledge of miRNAs’ roles in the process of HAND, and our findings provided potential therapeutic targets and clues of HAND.

The purpose of this study was to identify the factors that affect the mortality among adult HIV/TB co-infected patients and to see the nutritional difference among mortality in residence level. Retrospective cohort studies of 417 patients which fulfill our criteria were included. Multilevel logistic regression models were used. MLwiN and SPSS software are used to estimate the parameter. The variance of the random factor in the empty model was significant which indicates that there were residential differences in TB-HIV co-infected mortality and it shows multilevel analysis was an appropriate approach for further analysis. The prevalence of HIV/TB co-infected patients' death was 12.9% in study time. Functional status, age of patients, WHO clinical stages, nutritional status, CD4 counts, regimen, and BMI were found to be significant determinants of HIV/TB co-infected mortality. In our study, patients with the bedridden category of functional status, the fourth stages of WHO clinical stages (stage IV), patients with higher age, patients whose treatments were second-line regimen and low CD4 cell counts were more at risk of death. The study also revealed that; poor nutritional status increased the risk of mortality among HIV/TB co-infected patients and it varies among the residence of the patients (rural area were more at risk).

Discriminatory attitudes towards people living with HIV/AIDS are prevalent. A Joint United Nations Program on HIV/AIDS report (2019) indicated that more than 50% of the people surveyed in one of the studies spanning 26 countries expressed unfavorable attitudes towards HIV-positive people. The objective of this study was to assess the attitudes of senior Education Studies students at a university in Spain towards people with HIV/AIDS so as to propose specific educational interventions. The study employed a quantitative methodological approach; a questionnaire with a 14-item attitude score served as the analytical instrument. The study sample comprised 613 students from the School of Education at the University of Huelva, Spain. The results showed that more than 50% of the School’s senior students had discriminatory attitudes towards HIV-positive people, some of whom were fellow classmates. This study proposes several formative approaches to reducing the stigma suffered by HIV-positive people, while also improving senior students’ skills and capabilities in the field of health promotion.

Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding have been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

The HIV-1 nef gene terminates in a 3’-UGA stop codon, which is highly conserved in the main group of HIV-1 subtypes, along with a downstream potential coding region that could extend the nef protein by 33 amino acids, if readthrough of the stop codon occurs. Antisense tethering interactions (ATIs) between a viral mRNA and a host selenoprotein mRNA are a potential viral strategy for the capture of a host selenocysteine insertion sequence (SECIS) element (Taylor et al, 2016) [1]. This mRNA hijacking mechanism could enable the expression of virally encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine (SeC). Here we show that readthrough of the 3’-terminal UGA codon of nef occurs during translation of HIV-1 nef expression constructs in transfected cells. This was accomplished via fluorescence microscopy image analysis and flow cytometry of HEK 293 cells, transfected with engineered GFP reporter gene plasmid constructs, in which GFP can only be expressed by translational recoding of the UGA codon. SiRNA knockdown of thioredoxin reductase 1 (TR1) mRNA resulted in a 67% decrease in GFP expression, presumably due to reduced availability of the components involved in selenocysteine incorporation for the stop codon readthrough, thus supporting the proposed ATI. Addition of 20 nM sodium selenite to the media significantly enhanced stop codon readthrough in the pNefATI1 plasmid construct, by >100%, supporting the hypothesis that selenium is involved in the UGA readthrough mechanism.

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

DNA vaccines are stable, safe, cost effective to produce and relatively quick and easy to manufacture. However, to date DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits and macaques, at 4 to 10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.

Cowpea chlorotic mottle virus (CCMV) is a plant virus explored as a nanotechnological platform. The robust self-assembly mechanism of its capsid protein allows for drug encapsulation and targeted delivery. Additionally, the capsid nanoparticle can be used as a programmable platform to display different molecular moieties. In view of future applications, efficient production and purification of plant viruses is a key step. In established protocols, the need for ultracentrifugation is a significant limitation due to cost, difficult scalability, and safety issues. In addition, the purity of the final virus isolate often remains unclear. Here, an advanced protocol for the purification of CCMV from infected plant tissue was developed, focusing on efficiency, economy, and final purity. The protocol involves precipitation with PEG 8000, followed by an affinity extraction using a novel peptide aptamer. The efficiency of the protocol was validated using size exclusion chromatography, MALDI-TOF mass spectrometry, reversed-phase HPLC, and sandwich immunoassay. It was demonstrated that the final eluate of the affinity column is of exceptional purity (98.4%) determined by HPLC and detection at 220 nm. The scale-up of our proposed method seems to be straightforward, which opens the way to the large-scale production of such nanomaterials. This highly improved protocol may facilitate the use and implementation of plant viruses as nanotechnological platforms for in vitro and in vivo applications.

SARS-CoV-2, influenza A/B virus (IAV/IBV) and respiratory syncytial virus (RSV) are among the common viruses causing acute respiratory infections. Clinical diagnosis to differentiate these viruses is challenging due to similar clinical presentations, thus laboratory-based real-time RT PCR is the gold standard for diagnosis. The study aimed to evaluate the diagnostic performance of STANDARD M10 Flu/RSV/SARS-CoV-2 (SD Biosensor Inc, Seoul, Korea). This retrospective study was conducted with archived respiratory samples positive and negative for SARS-CoV-2, IAV, IBV or RSV. The evaluation study involved a total of 322 respiratory samples comprising 215 positive samples (49 SARS-CoV-2, 48 IAV, 53 IBV, 65 RSV) and 107 negative samples. All samples were tested with both STANDARD M10 and either Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV (Cepheid, USA). The sensitivity, specificity, positive predictive value and negative predictive value rates of STANDARD M10 were very similar to Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV ranges for each virus (98-100%). The overall agreement was 99.4% with 99.1% agreement for positive samples and 100% agreement for negative samples. In conclusion, the STANDARD M10 point-of-care test is suitable for rapid simultaneous detection of SARS-CoV-2, IAV, IBV and RSV.

Hepatitis B virus (HBV) remains a dominant cause of hepatocellular carcinoma (HCC). Recently it was shown that HBV and woodchuck hepatitis virus (WHV) integrate into hepatocyte genome minutes after invasion. Retrotransposons and transposable sequences were frequent sites of the initial insertions suggesting a mechanism for spontaneous HBV DNA disperse throughout hepatocyte genome. Several somatic genes were also identified as early insertional targets in infected hepatocytes and woodchuck livers. Head-to-tail joints (HTJs) dominated amongst fusions indicating their creation by non-homologous-end-joining (NHEJ). Their formation coincided with robust oxidative damage of hepatocyte DNA. This was associated with activation of the poly(ADP-ribose) polymerase 1 (PARP1)-mediated dsDNA repair as reflected by augmented transcription of PARP1 and XRCC1, the PARP1 binding partner, OGG1, a responder to oxidative DNA damage, and by increased activity of NAD+, a marker of PARP1 activation, and HO1, an indicator of cell oxidative stress. The engagement of the PARP1-mediated NHEJ repair pathway explains HTJ format of the initial merges. The findings showed that HBV and WHV are immediate inducers of oxidative DNA damage, hijack dsDNA repair to integrate into hepatocyte genome and by this may initiate pro-oncogenic process. Tracking initial integrations may uncover early markers of HCC and help to explain HBV-associated oncogenesis.

Jingmen viruses are newly described segmented flavi-like viruses that have a worldwide distribution in ticks and have been associated with febrile illnesses in humans. Computational analyses were used to predict that Jingmen flavi-like virus glycoproteins have structural features of class II viral fusion proteins, including an ectodomain consisting of beta-sheets and short alpha-helices, a fusion peptide with interfacial hydrophobicity and a three domain architecture. Jingmen flavi-like virus glycoproteins have a sequence enriched in serine, threonine and proline at the amino terminus, which is a feature of mucin-like domains. Several of the serines and threonines are predicted be modified by the addition of O-linked glycans. Some of the glycoproteins are predicted to have an additional mucin-like domain located prior to the transmembrane anchor, whereas others are predicted to have a stem consisting of two alpha-helices. The flavivirus envelope protein and Jingmen flavi-virus glycoproteins may have diverged from a common class II precursor glycoprotein with a mucin-like domain or domains acquired after divergence.

Background and Aim: Spontaneous bacterial peritonitis is a common infection in liver cirrhosis. This systematic review and meta-analysis provides detailed information on the prevalence of SBP among HBV and HCV-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV, and HCV related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1,713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7 – 21.0%; I2= 96.13%; p < 0.001)], followed by SBP in HCV associated liver cirrhosis [4.0% (95% CI, 1.3% – 11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1 – 66.3%), the USA (50.0%, CI: 34.6 – 65.4%), and Holland (31.1%, CI: 21.6 – 42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV+HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P<0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed an increase in the incidence of SBP in viral hepatitis over the last decade, the latter could be due to the global increase in Bacterial resistance. This indicates a possible future rise in the global prevalence of SBP among HBV, and HCV-related liver cirrhosis.

The irregular timing and spatial variation in zoonotic arbovirus spillover from vertebrate hosts to humans and livestock present challenges to predicting their occurrence from year to year and within their broader geographic range, compromising effective prevention and control strategies. The objective of this study was to quantify effects of landscape composition and configuration and dynamic temperature and precipitation values on the 2018 spatiotemporal distribution of eastern equine encephalitis virus (EEEV) (Togaviridae, Alphavirus) and West Nile virus (WNV) (Flaviviridae, Flavivirus) sentinel chicken seroconversion in northeastern Florida using Earth Observation (EO) data and a modeling framework that incorporated joint spatial and temporal effects. We investigated environmental effects using Bernoulli generalized linear mixed effects models (GLMMs) including a site level random effect, and then added spatial random effects and spatiotemporal random effects in subsequent runs. Models were executed using integrated nested Laplace approximation (INLA) and a stochastic partial differential equation (SPDE) approach in R-INLA. GLMMs that included a spatiotemporal random effect performed better relative to models that included only spatial random effects and better than non-spatial models. Results indicated strong spatiotemporal structure in seroconversion for both viruses, but EEEV exhibited more punctuated and compact structure at the beginning of the sampling season, while WNV exhibited more gradual and diffuse structure across the study area toward the end of the sampling season. Percentage of cypress/tupelo wetland land cover within 3500 m of coop sites and edge density of forest land cover within 500 m had a strong positive effect on EEEV seroconversion, while the best fitting model for WNV was the intercept only model with spatiotemporal random effects. Lagged temperature and precipitation variables included in our study did not have a strong effect on seroconversion for either virus when accounting for temporal autocorrelation, demonstrating the utility of capturing this structure to avoid Type I errors. Predictive accuracy on out-of-sample data for EEEV seroconversion demonstrates the potential to develop a temporally dynamic framework to predict arbovirus transmission.

The interaction of human immunodeficiency virus with human cells is responsible for all stages of the viral life cycle, from the infection of CD4+ cells to reverse transcription, integration, and the assembly of new viral particles. To date, a large amount of OMICs data as well as information from functional genomics screenings regarding the HIV-1-host interaction has been accumulated in the literature and in public databases. We processed databases containing HIV-host interactions and found 2910 HIV-1-human protein-protein interactions, mostly related to viral group M subtype B, 137 interactions between human and HIV-1 coding and non-coding RNAs, essential for viral lifecycle and cell defense mechanisms, 232 transcriptomics, 27 proteomics, and 34 epigenomics HIV-related experiments. Numerous studies regarding network-based analysis of corresponding OMICs data have been published in recent years. We overview various types of molecular networks, which can be created using OMICs data, including HIV-human protein-protein interaction networks, co-expression networks, gene regulatory and signaling networks, and approaches for the analysis of their topology and dynamics. The network-based analysis can be used to determine the critical pathways and key proteins involved in the HIV life cycle, cellular and immune responses to infection, viral escape from host defense mechanisms, and mechanisms mediating different susceptibility of humans to infection. The proteins and pathways identified in these studies may represent a basis for developing new anti-HIV therapeutic strategies such as new small-molecule drugs preventing infection of CD4+ cells and viral replication, effective vaccines, "shock and kill" and "block and lock" approaches to cure latent infection.

Canine infectious respiratory disease complex (CIRDC) is caused by different viruses and bacteria. Viruses associated with CIRDC include canine adenovirus-2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine herpesvirus (CHV), canine coronavirus (CCoV) and canine parainfluenza virus (CPIV). Bacteria associated with CIRDC include Bordetella bronchiseptica, Streptococcus equi subspecies zooepidemicus, and Mycoplasma spp. The present study examined the prevalence of pathogens associated with CIRDC in specimens received by a Veterinary Diagnostic Laboratory in Georgia from 2018 to 2022. Out of 459 cases, viral agents were detected in 34% cases and bacterial agents were detected in 58% cases. A single pathogen was detected in 31% cases, while two or more pathogens were identified in 24% cases. The percentages of viral agents identified were CAV-2 (4%), CDV (3%), CPIV (16%), CCoV (7%), and CIV (2%). The percentages of bacterial agents were Bordetella bronchiseptica (10%), Mycoplasma canis (24%), Mycoplasma cynos (21%), and S treptococcus zooepidemicus (2%). Positive viral cases ranged from 2-4% for CAV-2, 1-7% for CDV, 1-4% for CHV, 9-22% for CPIV, 4-13% for CCoV, and 1-4% for CIV. Overall, the study showed that the most prevalent pathogens associated with CIRDC during the study period were CPIV, M. canis, and M. cynos.

The World Health Organization has estimated an annual occurrence of approximately 392 million Dengue virus (DENV) infections in more than 100 countries where the virus is endemic, and this represents a serious threat to humanity. DENV is a serologic group with four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) belonging to the genus Flavivirus, in the family Flaviviridae. Dengue is the most widespread mosquito-borne disease in the world. The ~10.7 kb DENV genome encodes three structural proteins (capsid [C], pre-membrane [prM], and envelope [E]) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The NS1 protein is a membrane-associated dimer and a secreted, lipid-associated hexamer. Dimeric NS1 is found on membranes both in cellular compartments and cell surfaces. Secreted NS1 (sNS1) is often present in patient serum at very high levels, which correlates with severe dengue symptoms. This study was conducted to discover how NS1 protein, microRNAs-15/16 (miRNAs-15/16), and apoptosis are related during DENV-4 infection in human liver cell lines. Huh 7.5 and HepG2 cells were infected with DENV-4, and miRNAs-15/16, viral load, NS1 protein, and caspases-3/7 were quantified after different times of infection. This study demonstrated that miRNAs-15/16 are overexpressed during infection of HepG2 and Huh 7.5 cells by DENV-4 and have a relationship with NS1 protein expression, viral load, and activity of caspases-3/7, thus making these miRNAs potential injury markers during DENV infection in human hepatocytes.

The Human Herpesviruses persist in the form of a latent infection in specialized cell types. During latency, the herpesvirus genomes associate with cellular histone proteins and the viral lytic genes assemble into transcriptionally repressive heterochromatin. Although there is divergence in the nature of heterochromatin on latent herpesvirus genomes, in general the genomes assemble into forms of heterochromatin that can convert to euchromatin to permit gene expression and therefore reactivation. This reversible form of heterochromatin is known as facultative heterochromatin and is most commonly characterized by polycomb silencing. Polycomb silencing is prevalent on the cellular genome and plays a role in developmentally regulated and imprinted genes, as well as X chromosome inactivation. As herpesviruses initially enter the cell in an un-chromatinized state, they provide an optimal system to study how de novo facultative heterochromatin is targeted to regions of DNA and how it contributes to silencing. Here, we describe how polycomb-mediated silencing potentially assembles onto herpesvirus genomes, synergizing what is known about herpesvirus latency with facultative heterochromatin targeting to the cellular genome. A greater understanding of polycomb silencing of herpesviruses will inform on the mechanism of persistence and reactivation of these pathogenic human viruses and provide clues regarding how de novo facultative heterochromatin forms on the cellular genome.

Novel Coronavirus infection mediated pandemic started in China in December 2019 and is still killing 1000s of people throughout the world. The second most populous country, India too is fighting against this infectious disease. The country is taking effective measures to curb the pandemic by exerting extensive campaigning on sanitation and strict social distancing measures to quell the explosion of the infection rate. The future of the COVID-19 infections in India still remain unpredictable, so precautionary methods need to be continued until the growth rate of new cases drop below one.

The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non- canonical latency program of EBV with an activated PD-L1 pathway. In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

For many years marine algae has been subject of numerous researches and as a source of natural products with antiviral activity, such as terpenes, alkaloids and sulphated polysaccharides. However, the anti-Zika virus (ZIKV) potential of algae has not been studied. In this study we evaluated extracts seven species of the three major classes of seaweeds (Phaeophyceae, Chlorophyceae and Rhodophyceae) against ZIKV. All seaweeds tested are native of the Brazilian coast, except for Kappaphycus alvarezii that can be cultivated. ZIKV a mosquito-borne flavivirus, has become a public health problem. In recent years there has been an increase in the number of cases and a strong association between ZIKV outbreak and the spread of cases of Guillain-Barré Syndrome and microcephaly. All seaweed extracts tested in this work inhibits ZIKV replication in a dose-dependent manner. Caulerpa racemosa, Kappaphycus alvarezii and Osmundaria obtusiloba extracts were able to inhibit viral replication at low concentrations with EC₅₀ values ranging from 1.38 to 1.98 µg/mL. We observed that O. obtusiloba presented a significant virucidal effect. Our results suggest that extracts of C. racemosa, K. alvarezii and O. obtusiloba presented very promising results, being excellent candidates for further studies, demonstrating that marine algae are an interesting source for the development of novel anti-ZIKV agents.

Cryptosporidiosis is one of the most important causes of gastroenteritis in the world, especially in low- and middle-income countries. It is caused by the Apicomplexan parasite Cryptosporidium spp., and mainly affects children and immunosuppressed people, in whom it can pose a serious risk to their health, or even be life-threatening. In Honduras there are no data on parasite species or on molecular diversity or Cryptosporidium subtypes. Therefore, a cross-sectional study was conducted between September 2019 and March 2020 for the molecular identification of Cryptosporidium spp. in 102 patients living with HIV who attended a national hospital in Tegucigalpa. Stool samples were analysed by direct microscopy, acid-fast stained smears, and a rapid lateral flow immunochromatographic test. All samples that tested positive were molecularly analyzed to identify the species and subtype of the parasite using three different markers: gp60, cowp, and 18Sr. PCR products were also sequenced. Four out of 102 samples (3.92%) were positive for Cryptosporidium parvum, and all were assigned to subtype IIa. These findings suggest a possible zoonotic transmission in this population.

The tiered laboratory framework for HIV viral load monitoring accommodates a range of HIV viral load testing platforms, with quality assessment critical to ensure quality patient testing. HIV plasma viral load testing is challenged by the instability of viral RNA. An approach using an RNA stabilizing buffer is described for the Xpert® HIV-1 Viral Load (Cepheid) assay and was tested in remote laboratories in South Africa. EDTA-plasma panels with known HIV viral titres were prepared in PrimeStore molecular transport medium for per-module verification and per-instrument external quality assessment. The panels were transported at ambient temperatures to 13 testing laboratories during 2017 and 2018, tested according to standard procedures and uploaded to a web portal for analysis. A total of 275 quality assessment specimens (57 verification panels and two EQA cycles) were tested. All participating laboratories met study verification criteria (n=171 specimens) with an overall concordance correlation coefficient (ρ_c) of 0.997 (95% confidence interval [CI]: 0.996 to 0.998) and a mean bias of -0.019 log cp/mL (95% CI: -0.044 to 0.063). The overall EQA ρ_c (n=104 specimens) was 0.999 (95% CI: 0.998 to 0.999), with a mean bias of 0.03 log cp/mL (95% CI: 0.02 to 0.05). These panels are suitable for use in quality monitoring of Xpert® HIV-1 VL and are applicable to laboratories in remote settings.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral Integrase (IN) enzyme catalyses integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of Integrase Strand Transfer Inhibitors (INSTIs). In this study, we applied computational methods of molecular modelling and docking to analyse the effect of NOPs on the full-length IN structure and INSTI binding. We identified 16 NOPs within the Cameroonian derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any effect on INSTI binding. INSTIs displayed similar binding affinities to each IN structure. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment naïve populations. This study supports the use of second-generation INSTI DTG as part of first-line combination antiretroviral therapy (cART) regimens, due to DTG possessing a stronger genetic barrier to the emergence of drug resistance.

For the diagnosis of disease, the ability to quantitatively detect trace amounts of the causal proteins from bacteria/viruses as biomarkers in patient specimens is highly desirable. Here we introduce a simple, rapid, and colorimetric assay as a de novo, ultrasensitive detection method. This ultrasensitive assay consists of sandwich enzyme-linked immunosorbent assay (ELISA) and thionicotinamide-adenine dinucleotide (thio-NAD) cycling, forming an ultrasensitive ELISA, in which the signal substrate (i.e., thio-NADH) accumulates in a triangular manner, and the accumulated thio-NADH is measured at its maximum absorption wavelength of 400 nm. We have successfully achieved a limit of detection of ca. 10–18 moles/assay for a target protein. As an example of infectious disease detection, HIV-1 p24 could be measured at 0.0065 IU/assay (i.e., 10⁻¹⁸ moles/assay), and as a marker for a lifestyle-related disease, adiponectin could be detected at 2.3 × 10⁻¹⁹ moles/assay. In particular, despite the long-held belief that the trace amounts of adiponectin in urine can only be detected using a radioisotope, our ultrasensitive ELISA was able to detect urinary adiponectin. This method is highly versatile, because simply changing the antibody enables the detection of various proteins. This assay system requires only the measurement of absorbance, thus it requires equipment that is easily obtained by medical facilities, which facilitates diagnosis in hospitals and clinics. Moreover, we describe an expansion of our ultrasensitive ELISA to a non-amplification nucleic acid detection method for nucleic acids using hybridization. These de novo methods will enable simple, rapid, and accurate diagnosis.

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices,PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER=$463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. Results suggest that boosting potential may be key to HIV vaccine value.