The mTOR Complex Controls HIV Latency

Emilie Besnard, Shweta Hakre, Martin Kampmann, Hyung W. Lim, Nina N. Hosmane, Alyssa Martin, Michael C. Bassik, Erik Verschueren, Emilie Battivelli, Jonathan Chan, J. Peter Svensson, Andrea Gramatica, Ryan J. Conrad, Melanie Ott, Warner C. Greene, Nevan J. Krogan, Robert F. Siliciano, Jonathan S. Weissman, Eric Verdin

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


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.

Original languageEnglish
Pages (from-to)785-797
Number of pages13
JournalCell Host and Microbe
Issue number6
StatePublished - 14 Dec 2016
Externally publishedYes


  • HIV latency
  • HIV transcription
  • genome-wide shRNA screen
  • latency reversal
  • mTOR inhibition
  • reactivation from latency


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