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. Michael; Julie A. Ake; Sandhya Vasan; Denise C. Hsu; Beatrice H. Hahn; Frank Kirchhoff; Rasmi Thomas

doi:10.1126/scitranslmed.adg0873

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 journal › Article › peer-review

7 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 (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. 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 language	English
Article number	eadg0873
Journal	Science Translational Medicine
Volume	15
Issue number	707
DOIs	https://doi.org/10.1126/scitranslmed.adg0873
State	Published - 2023
Externally published	Yes

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Geretz, A., Ehrenberg, P. K., Clifford, R. J., Laliberté, A., Bozzo, C. P., Eiser, D., Kundu, G., Yum, L. K., Apps, R., Creegan, M., Gunady, M., Shangguan, S., Sanders-Buell, E., Sacdalan, C., Phanuphak, N., Tovanabutra, S., Russell, R. M., Bibollet-Ruche, F., Robb, M. L., ... Thomas, R. (2023). Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo. Science Translational Medicine, 15(707), Article eadg0873. https://doi.org/10.1126/scitranslmed.adg0873

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title = "Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo",

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.",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved;",

year = "2023",

doi = "10.1126/scitranslmed.adg0873",

language = "English",

volume = "15",

journal = "Science Translational Medicine",

issn = "1946-6234",

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Geretz, A, Ehrenberg, PK, Clifford, RJ, Laliberté, A, Bozzo, CP, Eiser, D, Kundu, G, Yum, LK, Apps, R, Creegan, M, Gunady, M, Shangguan, S, Sanders-Buell, E, Sacdalan, C, Phanuphak, N, Tovanabutra, S, Russell, RM, Bibollet-Ruche, F, Robb, ML, Michael, NL , Ake, JA, Vasan, S, Hsu, DC, Hahn, BH, Kirchhoff, F & Thomas, R 2023, 'Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo', Science Translational Medicine, vol. 15, no. 707, eadg0873. https://doi.org/10.1126/scitranslmed.adg0873

TY - JOUR

T1 - Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo

AU - Geretz, Aviva

AU - Ehrenberg, Philip K.

AU - Clifford, Robert J.

AU - Laliberté, Alexandre

AU - Bozzo, Caterina Prelli

AU - Eiser, Daina

AU - Kundu, Gautam

AU - Yum, Lauren K.

AU - Apps, Richard

AU - Creegan, Matthew

AU - Gunady, Mohamed

AU - Shangguan, Shida

AU - Sanders-Buell, Eric

AU - Sacdalan, Carlo

AU - Phanuphak, Nittaya

AU - Tovanabutra, Sodsai

AU - Russell, Ronnie M.

AU - Bibollet-Ruche, Frederic

AU - Robb, Merlin L.

AU - Michael, Nelson L.

AU - Ake, Julie A.

AU - Vasan, Sandhya

AU - Hsu, Denise C.

AU - Hahn, Beatrice H.

AU - Kirchhoff, Frank

AU - Thomas, Rasmi

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85166421544&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.adg0873

DO - 10.1126/scitranslmed.adg0873

M3 - Article

C2 - 37531416

AN - SCOPUS:85166421544

SN - 1946-6234

VL - 15

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 707

M1 - eadg0873

ER -

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

Abstract

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