Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genetic Characterization of HIV-1 tat Gene from Virologically Controlled HIV-infected Older Patients on Long-term Antiretroviral Therapy

Version 1 : Received: 1 October 2023 / Approved: 2 October 2023 / Online: 2 October 2023 (11:55:01 CEST)

How to cite: Kummet, N.; Mishra, N.; Diaz, A.; Cusick, N.; Klotz, S. A.; Ahmad, N. Genetic Characterization of HIV-1 tat Gene from Virologically Controlled HIV-infected Older Patients on Long-term Antiretroviral Therapy. Preprints 2023, 2023100046. https://doi.org/10.20944/preprints202310.0046.v1 Kummet, N.; Mishra, N.; Diaz, A.; Cusick, N.; Klotz, S. A.; Ahmad, N. Genetic Characterization of HIV-1 tat Gene from Virologically Controlled HIV-infected Older Patients on Long-term Antiretroviral Therapy. Preprints 2023, 2023100046. https://doi.org/10.20944/preprints202310.0046.v1

Abstract

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.

Keywords

HIV+ older patients; ART; tat sequences; genetic diversity; CTL epitopes

Subject

Biology and Life Sciences, Virology

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