AP-1/c-Fos supports SIV and HIV-1 latency in CD4 T cells infected in vivo
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
Affiliations
Viviana Cobos Jiménez
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
Aviva Geretz
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
Andrey Tokarev
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
Philip K. Ehrenberg
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
Selase Deletsu
George Washington University, Washington, DC, USA
Kawthar Machmach
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
Prakriti Mudvari
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
J. Natalie Howard
George Washington University, Washington, DC, USA
Amanda Zelkoski
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
Dominic Paquin-Proulx
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
Gregory Q. Del Prete
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
Caroline Subra
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
Eli A. Boritz
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Alberto Bosque
George Washington University, Washington, DC, USA
Rasmi Thomas
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Corresponding author
Diane L. Bolton
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; Corresponding author
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.
