ArticleCell host & microbe2016
The mTOR Complex Controls HIV Latency.
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Article in Cell host & microbe, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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155citing papers in PubMed
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Who cites it
155 citing papers in PubMed, 196 citations in OpenAlex.
- Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations.The Journal of clinical investigation · 2020Trial
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- Single-cell capture of on-ART SIV transcription reveals TGF-β-mediated metabolic control of viral latency.JCI insight · 2026Article
- Tools to Quantify and Characterize the Persistent Reservoir in People with HIV-1: Focus on Non-B Subtypes.Viruses · 2026Review
- Dynamics of HIV reservoirs following repeated anti-SARS-CoV-2 vaccination.Frontiers in immunology · 2026Review
- Host restriction factors and p17-Driven inflammaging in HIV-1: From molecular pathogenesis to functional cure.AIMS microbiology · 2026Review
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- HIV-induced T cell quiescence and the origins of viral latency.Nature immunology · 2025Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Immuno-cell metabolic changes in HIV-1 infection.Infectious diseases & immunity · 2025Review
- Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.Drug delivery and translational research · 2025Review
- PADI4-mediated citrullination of histone H3 stimulates HIV-1 transcription.Nature communications · 2025Article
- Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HIV-1 Nef activates proviral DNA transcription by recruiting Src kinase to phosphorylate host protein Nef-associated factor 1 to compromise its viral restrictive function.Journal of virology · 2025Article
- Targeting Ikaros and Aiolos with pomalidomide fails to reactivate or induce apoptosis of the latent HIV reservoir.Journal of virology · 2025Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 2 countries.
Emilie BesnardGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Shweta HakreGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Martin KampmannDepartment of Cellular and Molecular Pharmacology, The California Institute for Quantitative Biomedical Research, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Hyung W LimGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Nina N HosmaneDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
Alyssa MartinDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
Michael C BassikDepartment of Cellular and Molecular Pharmacology, The California Institute for Quantitative Biomedical Research, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Erik VerschuerenDepartment of Cellular and Molecular Pharmacology, The California Institute for Quantitative Biomedical Research, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Emilie BattivelliGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Jonathan ChanGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
J Peter SvenssonKarolinska Institutet, Department of Biosciences and Nutrition, Novum, 141 83 Huddinge, Sweden.
Andrea GramaticaGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Ryan J ConradGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Melanie OttGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Warner C GreeneGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Nevan J KroganGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, The California Institute for Quantitative Biomedical Research, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Robert F SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
Jonathan S WeissmanDepartment of Cellular and Molecular Pharmacology, The California Institute for Quantitative Biomedical Research, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Eric VerdinGladstone Institute of Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: everdin@gladstone.ucsf.edu.
University of California, San Francisco · USGladstone Institutes · USHoward Hughes Medical Institute · USJohns Hopkins Medicine · USJohns Hopkins University · USKarolinska Institutet · SE
Funding
Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Monica Gandhi · 1988 to 2026
$93.6MX-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2007 to 2018
$48.8MTraining Program in Cellular and Molecular MedicineT32GM008752 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2000 to 2019
$11.7MMolecular Mechanisms of HIV LatencyR01DA041742 · NIDA · J. DAVID GLADSTONE INSTITUTES · PI VERDIN, ERIC M. · 2016 to 2021
$6.5MNovel Model for HIV Latency in Primary Memory T CellsDP1DA031126 · NIDA · J. DAVID GLADSTONE INSTITUTES · PI VERDIN, ERIC M. · 2010 to 2014
$4.7MNovel model for HIV Latency in Oral Primary Lymphoid TissuesR01DE026010 · NIDCR · J. DAVID GLADSTONE INSTITUTES · PI VERDIN, ERIC M. · 2016 to 2020
$4.2MIdentification of HIV latency biomarkers with a dual fluorescence reporter HIVR01AI117864 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI VERDIN, ERIC M. · 2015 to 2020
$3.5MEpigenetic regulation of HIV latencyR01DA030216 · NIDA · J. DAVID GLADSTONE INSTITUTES · PI VERDIN, ERIC M. · 2010 to 2014
$2.6MRewiring of the human protein homeostasis network in normal and disease contextsDP2GM119139 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN · 2015 to 2015
$2.3MBD FACSAria II Flow CytometerS10RR028962 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI CAVROIS, MARIELLE · 2011 to 2011
$544kNCRR NIH HHS S10 RR028962NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI117864NIDA NIH HHS DP1 DA031126NIDA NIH HHS R01 DA030216NIDA NIH HHS R01 DA041742NIDCR NIH HHS R01 DE026010NIGMS NIH HHS DP2 GM119139NIGMS NIH HHS P50 GM082250NIGMS NIH HHS T32 GM008752
Abstract
A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells. mTOR inhibitors suppress HIV transcription both through the viral transactivator Tat and via Tat-independent mechanisms. This inhibition occurs at least in part via blocking the phosphorylation of CDK9, a p-TEFb complex member that serves as a cofactor for Tat-mediated transcription. The control of HIV latency by mTOR signaling identifies a pathway that may have significant therapeutic opportunities.
Indexed as
Adaptor Proteins, Signal TransducingCD4-Positive T-LymphocytesCell LineClustered Regularly Interspaced Short Palindromic RepeatsCyclin-Dependent Kinase 9Gene Expression Regulation, ViralGene Knockdown TechniquesGenes, ViralHIV-1HIV InfectionsHumansK562 CellsmTOR Associated Protein, LST8 HomologPhosphorylationPositive Transcriptional Elongation Factor BRNA, Small InterferingAdaptor Proteins, Signal TransducingCDK9 protein, humanCyclin-Dependent Kinase 9MLST8 protein, humanmTOR Associated Protein, LST8 HomologPositive Transcriptional Elongation Factor BRNA, Small Interferingtat Gene Products, Human Immunodeficiency VirusTOR Serine-Threonine Kinasesgenome-wide shRNA screenHIV latencyHIV LTRHIV transcriptionlatency reversalmTOR inhibitionreactivation from latency
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