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

Aviva Geretz, Philip K. Ehrenberg, Robert J. Clifford, Alexandre Laliberté, Caterina Prelli Bozzo, Daina Eiser, Gautam Kundu, Lauren K. Yum, Richard Apps, Matthew Creegan, Mohamed Gunady, Shida Shangguan, Eric Sanders-Buell, Carlo Sacdalan, Nittaya Phanuphak, Sodsai Tovanabutra, Ronnie M. Russell, Frederic Bibollet-Ruche, Merlin L. Robb, Nelson L. MichaelJulie A. Ake, Sandhya Vasan, Denise C. Hsu, Beatrice H. Hahn, Frank Kirchhoff, Rasmi Thomas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 (Padjusted < 0.05) and was validated in 28 additional participants from Thailand and the Americas with HIV-1 CRF01_AE and subtype B infections, respectively. Over-expression 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.

Original languageEnglish
Article numbereadg0873
JournalScience Translational Medicine
Volume15
Issue number707
DOIs
StatePublished - 2023
Externally publishedYes

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