The mTOR Complex Controls HIV Latency.
The mTOR Complex Controls HIV Latency.
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DOI：
10.1016/j.chom.2016.11.001
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发表时间：
2016-12-14
影响因子：
30.3
通讯作者：
Verdin E
中科院分区：
文献类型：
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作者：
Besnard E;Hakre S;Kampmann M;Lim HW;Hosmane NN;Martin A;Bassik MC;Verschueren E;Battivelli E;Chan J;Svensson JP;Gramatica A;Conrad RJ;Ott M;Greene WC;Krogan NJ;Siliciano RF;Weissman JS;Verdin E
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 as well as 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.
