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