The mTOR Complex Controls HIV Latency. Academic Article uri icon

Overview

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.

publication date

  • December 14, 2016

Research

keywords

  • HIV Infections
  • HIV-1
  • TOR Serine-Threonine Kinases
  • Virus Latency

Identity

PubMed Central ID

  • PMC5354304

Scopus Document Identifier

  • 85006141771

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2016.11.001

PubMed ID

  • 27978436

Additional Document Info

volume

  • 20

issue

  • 6