Variation in HIV-1 Tat activity is a key determinant in the establishment of latent infection

• DOI: 10.1172/jci.insight.184711
• Publication Date: 2024-12-05T17:00:27Z
• Authors: Francisco Gomez-R...; Valeri H. Terry; Cuie Chen; Mark M. Painter; Maria C. Virgilio; Marianne E. Yaple...; Kathleen L. Collins
• Keywords: Provirus; SAMHD1; Virus latency; Transcription

Despite effective treatment, Human immunodeficiency virus (HIV) persists in optimally treated people as a transcriptionally silent provirus. Latently infected cells evade the immune system and harmful effects of virus, thereby creating long-lasting reservoir HIV. To gain deeper insight into molecular mechanisms HIV latency establishment, we constructed series HIV-1 fluorescent reporter viruses that distinguish active versus latent infection. We unexpectedly observed proportion active-to-latent infection depended on limiting viral factor, which created bottle neck could be overcome by superinfection cell, T cell activation or overexpression trans activator transcription (Tat). In addition, found tat rev expression levels vary amongst clones were an important variable establishment. Lower limited protein whereas lower Tat mutation binding element promoted was resistant to reactivation even fully activated primary cells. Nevertheless, combinations reversal agents targeting both cellular histone acetylation pathways overcame deficiencies Tat-TAR axis regulation. These results provide additional establishment inform Tat-centered approaches cure