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

Authors

• Viviana Cobos Jiménez, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
• Aviva Geretz, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
• Andrey Tokarev, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, 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.
• 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.
• Dominic Paquin-Proulx, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, 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.
• 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.
• Diane L. Bolton, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Document Type

Journal Article

Publication Date

10-20-2023

Journal

iScience

Volume

26

Issue

10

DOI

10.1016/j.isci.2023.108015

Keywords

Immunology; Microbiology; Molecular biology

Abstract

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 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 a component of the Activator protein 1 (AP-1) transcription factor, relative to vRNA-low and -negative cells. Conversely, and , 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.

APA Citation

Cobos Jiménez, Viviana; Geretz, Aviva; Tokarev, Andrey; Ehrenberg, Philip K.; Deletsu, Selase; Machmach, Kawthar; Mudvari, Prakriti; Howard, J Natalie; Zelkoski, Amanda; Paquin-Proulx, Dominic; Del Prete, Gregory Q.; Subra, Caroline; Boritz, Eli A.; Bosque, Alberto; Thomas, Rasmi; and Bolton, Diane L., "AP-1/c-Fos supports SIV and HIV-1 latency in CD4 T cells infected" (2023). GW Authored Works. Paper 3570.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3570

Department

Microbiology, Immunology, and Tropical Medicine