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Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo.
Geretz, Aviva; Ehrenberg, Philip K; Clifford, Robert J; Laliberté, Alexandre; Prelli Bozzo, Caterina; Eiser, Daina; Kundu, Gautam; Yum, Lauren K; Apps, Richard; Creegan, Matthew; Gunady, Mohamed; Shangguan, Shida; Sanders-Buell, Eric; Sacdalan, Carlo; Phanuphak, Nittaya; Tovanabutra, Sodsai; Russell, Ronnie M; Bibollet-Ruche, Frederic; Robb, Merlin L; Michael, Nelson L; Ake, Julie A; Vasan, Sandhya; Hsu, Denise C; Hahn, Beatrice H; Kirchhoff, Frank; Thomas, Rasmi.
Afiliación
  • Geretz A; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Ehrenberg PK; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Clifford RJ; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Laliberté A; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Prelli Bozzo C; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Eiser D; Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.
  • Kundu G; Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.
  • Yum LK; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Apps R; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Creegan M; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Gunady M; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Shangguan S; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Sanders-Buell E; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Sacdalan C; NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD 20892, USA.
  • Phanuphak N; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Tovanabutra S; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Russell RM; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Bibollet-Ruche F; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Robb ML; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Michael NL; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Ake JA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Vasan S; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
  • Hsu DC; SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand.
  • Hahn BH; SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand.
  • Kirchhoff F; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Thomas R; Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA.
Sci Transl Med ; 15(707): eadg0873, 2023 08 02.
Article en En | MEDLINE | ID: mdl-37531416
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. 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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos