Hokello, JosephLakhikumar Sharma, AdhikarimayumTyagi, Mudit2022-12-052022-12-052020Hokello, J., Sharma, A. L., & Tyagi, M. (2020). Efficient Non-Epigenetic Activation of HIV Latency through the T-Cell Receptor Signalosome. Viruses, 12(8), 868.https://www.mdpi.com/792652https://nru.uncst.go.ug/handle/123456789/5889Human immunodeficiency virus type-1 (HIV-1) can either undergo a lytic pathway to cause productive systemic infections or enter a latent state in which the integrated provirus remains transcriptionally silent for decades. The ability to latently infect T-cells enables HIV-1 to establish persistent infections in resting memory CD4+ T-lymphocytes which become reactivated following the disruption or cessation of intensive drug therapy. The maintenance of viral latency occurs through epigenetic and non-epigenetic mechanisms. Epigenetic mechanisms of HIV latency regulation involve the deacetylation and methylation of histone proteins within nucleosome 1 (nuc-1) at the viral long terminal repeats (LTR) such that the inhibition of histone deacetyltransferase and histone lysine methyltransferase activities, respectively, reactivates HIV from latency. Non-epigenetic mechanisms involve the nuclear restriction of critical cellular transcription factors such as nuclear factor-kappa beta (NF- B) or nuclear factor of activated T-cells (NFAT) which activate transcription from the viral LTR, limiting the nuclear levels of the viral transcription transactivator protein Tat and its cellular co-factor positive transcription elongation factor b (P-TEFb), which together regulate HIV transcriptional elongation. In this article, we review how T-cell receptor (TCR) activation e ciently induces NF- B, NFAT, and activator protein 1 (AP-1) transcription factors through multiple signal pathways and how these factors e ciently regulate HIV LTR transcription through the non-epigenetic mechanism. We further discuss how elongation factor P-TEFb, induced through an extracellular signal-regulated kinase (ERK)-dependent mechanism, regulates HIV transcriptional elongation before new Tat is synthesized and the role of AP-1 in the modulation of HIV transcriptional elongation through functional synergy with NF- B. FurthermoreenHIVnon-epigeneticstranscription factorslatencyreactivationArticle