Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo-Reference-Cited by-同舟云学术

Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo

Published:2023-08-02 Issue:707 Volume:15 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Geretz Aviva¹²^ORCID,Ehrenberg Philip K.¹^ORCID,Clifford Robert J.¹²^ORCID,Laliberté Alexandre³^ORCID,Prelli Bozzo Caterina³^ORCID,Eiser Daina¹²,Kundu Gautam¹²^ORCID,Yum Lauren K.¹²^ORCID,Apps Richard⁴^ORCID,Creegan Matthew¹²^ORCID,Gunady Mohamed¹²^ORCID,Shangguan Shida¹²^ORCID,Sanders-Buell Eric¹²,Sacdalan Carlo⁵^ORCID,Phanuphak Nittaya⁵^ORCID,Tovanabutra Sodsai¹²,Russell Ronnie M.⁶^ORCID,Bibollet-Ruche Frederic⁶,Robb Merlin L.¹²^ORCID,Michael Nelson L.⁷,Ake Julie A.¹^ORCID,Vasan Sandhya¹²^ORCID,Hsu Denise C.¹²^ORCID,Hahn Beatrice H.⁶^ORCID,Kirchhoff Frank³^ORCID,Thomas Rasmi¹^ORCID

Affiliation:

1. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

2. Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.

3. Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.

4. NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD 20892, USA.

5. SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand.

6. Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

7. Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

Abstract

Host restriction factors play key roles in innate antiviral defense, but it remains poorly understood which of them restricts HIV-1 in vivo. Here, we used single-cell transcriptomic analysis to identify host factors associated with HIV-1 control during acute infection by correlating host gene expression with viral RNA abundance within individual cells. Wide sequencing of cells from one participant with the highest plasma viral load revealed that intracellular viral RNA transcription correlates inversely with expression of the gene PTMA , which encodes prothymosin α. This association was genome-wide significant ( P adjusted < 0.05) and was validated in 28 additional participants from Thailand and the Americas with HIV-1 CRF01_AE and subtype B infections, respectively. Overexpression of prothymosin α in vitro confirmed that this cellular factor inhibits HIV-1 transcription and infectious virus production. Our results identify prothymosin α as a host factor that restricts HIV-1 infection in vivo, which has implications for viral transmission and cure strategies.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Link

https://www.science.org/doi/pdf/10.1126/scitranslmed.adg0873

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