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BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency.

BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency.
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Lu P, Shen Y, Yang H, Wang Y, Jiang Z, Yang X, Zhong Y, Pan H, Xu J, Lu H, Zhu H,


Lu P, Shen Y, Yang H, Wang Y, Jiang Z, Yang X, Zhong Y, Pan H, Xu J, Lu H, Zhu H, (click to view)

Lu P, Shen Y, Yang H, Wang Y, Jiang Z, Yang X, Zhong Y, Pan H, Xu J, Lu H, Zhu H,

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Scientific reports 2017 11 307(1) 16646 doi 10.1038/s41598-017-16816-1

Abstract

Persistent latent reservoir in resting CD4+ T cells is a major obstacle in curing HIV-1 infection. Effective strategies for eradication of the HIV-1 reservoir are urgently needed. We report here for the first time that two BET inhibitors, RVX-208, which has entered phase II clinical trials for diverse cardiovascular disorders, and PFI-1, which has been widely studied in oncology, can reactivate HIV-1 from latency. RVX-208 and PFI-1 treatment alone or in combination with other latency reversing agents efficiently reactivated HIV-1 transcription through an up-regulation of P-TEFb by increasing CDK9 Thr-186 phosphorylation in latently infected Jurkat T cells in vitro. The two BET inhibitors also reactivated HIV-1 transcription in cART treated patient-derived resting CD4+ T cells ex vivo, without influence on global immune cell activation. Our findings, in combination with previous reports, further confirm that BET inhibitors are a group of leading compounds for combating HIV-1 latency for viral eradication.

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