preprints.org > biology and life sciences > virology > doi: 10.20944/preprints202203.0216.v6

Preprint Article Version 6 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 13 March 2022 / Approved: 15 March 2022 / Online: 15 March 2022 (14:20:57 CET)
Version 2 : Received: 8 April 2022 / Approved: 11 April 2022 / Online: 11 April 2022 (08:43:41 CEST)
Version 3 : Received: 11 July 2022 / Approved: 12 July 2022 / Online: 12 July 2022 (08:07:43 CEST)
Version 4 : Received: 16 September 2022 / Approved: 16 September 2022 / Online: 16 September 2022 (11:45:33 CEST)
Version 5 : Received: 27 June 2023 / Approved: 28 June 2023 / Online: 28 June 2023 (16:13:16 CEST)
Version 6 : Received: 26 August 2023 / Approved: 28 August 2023 / Online: 29 August 2023 (09:31:10 CEST)

Recent studies revealing varied responses of infected cells to LRAs underscore the limited effectiveness of these agents and emphasize the wide array of determinants contributing to the heterogeneity of reservoirs, including virus genetic background, cell model, cell type, silencing mechanisms, tissue reservoirs, integration sites, patient, and gender specific factors. The enhancer region of the HIV-1 LTR contains two adjacent NF-κB binding sites that play a central role in mediating inducible HIV-1 gene expression. Beyond the involvement of various transcription factors, such as NF-κB, epigenetic constraints also play a pivotal role in suppressing the initiation of latent HIV transcription. Consequently, even latent viruses containing functional NF-κB sites remain unresponsive to drugs that activate NF-κB. Thus, it is evident that the activation of NF-κB alone does not suffice to trigger latent HIV, contradicting the central hypothesis of this study. The author used bioinformatics methods to analyze the viral proteins and their primer binding sites. The results show that the amino acid sequence ARG of Gag proteins of HTLV-1, HTLV-2, STLV-1 and STLV-2 match their primer binding site GGGGGCTCG in the 3'-to-5' direction and that the amino acid sequence SPR of Gag proteins of HIV-1, HIV-2, SIV and FIV match their primer binding site GGCGCCCGA in the 3'-to-5' direction. Related studies have shown that the genomic Gag/Gag-Pol complex recruits the LysRS/tRNA complex. The selective packaging of the tRNA primer requires HIV-1 Gag and Gag-Pol, and an interaction between LysRS and Gag is observed in vitro. In HIV-1, Gag/LysRS interaction depends on Gag sequences within the CTD of CA around amino acids 283-363 and motif 1 of LysRS around amino acids 208-259. It should be noted that the amino acid sequence SPR of the Gag protein is located at amino acids 148-150 within the NTD of CA, specifically at the NTD-NTD interface 1. Although this research is purely bioinformatics analysis, the relevant studies have demonstrated that Gag proteins match the HIV-1 primer binding site and possess the potential to directly activate dormant retroviruses.

HIV; HTLV; NF-κB; LysRS; Gag

Biology and Life Sciences, Virology

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