AP-1/c-Fos supports SIV and HIV-1 latency in CD4 T cells infected in vivo

Autor: Viviana Cobos Jiménez, Aviva Geretz, Andrey Tokarev, Philip K. Ehrenberg, Selase Deletsu, Kawthar Machmach, Prakriti Mudvari, J. Natalie Howard, Amanda Zelkoski, Dominic Paquin-Proulx, Gregory Q. Del Prete, Caroline Subra, Eli A. Boritz, Alberto Bosque, Rasmi Thomas, Diane L. Bolton
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iScience, Vol 26, Iss 10, Pp 108015- (2023)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2023.108015
Popis: Summary: Persistent HIV-1 reservoirs of infected CD4 T cells are a major barrier to HIV-1 cure, although the mechanisms by which they are established and maintained in vivo remain poorly characterized. To elucidate host cell gene expression patterns that govern virus gene expression, we analyzed viral RNA+ (vRNA) CD4 T cells of untreated simian immunodeficiency virus (SIV)-infected macaques by single-cell RNA sequencing. A subset of vRNA+ cells distinguished by spliced and high total vRNA (7–10% of reads) expressed diminished FOS, a component of the Activator protein 1 (AP-1) transcription factor, relative to vRNA-low and -negative cells. Conversely, FOS and JUN, another AP-1 component, were upregulated in HIV DNA+ infected cells compared to uninfected cells from people with HIV-1 on suppressive therapy. Inhibiting c-Fos in latently infected primary cells augmented reactivatable HIV-1 infection. These findings implicate AP-1 in latency establishment and maintenance and as a potential therapeutic target to limit HIV-1 reservoirs.
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