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


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.

SUBMITTER: Lu P 

PROVIDER: S-EPMC5709369 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Lu Panpan P   Shen Yinzhong Y   Yang He H   Wang Yanan Y   Jiang Zhengtao Z   Yang Xinyi X   Zhong Yangcheng Y   Pan Hanyu H   Xu Jianqing J   Lu Hongzhou H   Zhu Huanzhang H  

Scientific reports 20171130 1


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 a  ...[more]

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