Journal
BIOCHEMICAL PHARMACOLOGY
Volume 164, Issue -, Pages 237-251Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2019.04.005
Keywords
Latent HIV-1; Shock and kill; Latency-reversing agent; CPI-203; p-TEFb
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Funding
- Natural Science Foundation of China [81673481, 81773787]
- Guangzhou Baiyun District Science and Technology Program Project [2016-KJ-002]
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The persistence of latent human immunodeficiency virus type 1 (HIV-1) reservoirs remains a major hurdle for HIV-1 eradication. The shock and kill strategy relies on the drug-mediated reversion of HIV-1 latency and the subsequent death of HIV-producing cells. Unfortunately, none of the agents currently in use possess a sufficient potency to reactivate latent virus or eliminate the latent HIV-1 reservoir in vivo. Here, we demonstrated that a promising specific bromodomain and extraterminal domain inhibitor, CPI-203, could potently reactivate latent HIV-1 in different latently infected cell lines with minimal cytotoxicity by activating the positive transcription elongation factor b signaling pathway. Notably, CPI-203 exhibited synergism in latent HIV-1 reactivation and alleviated the HIV-1-induced cytokine storm when used in combination with the protein kinase C (PKC) agonist prostratin. These findings highlight that CPI-203 shows promise as a novel, safe candidate for the design of targeted strategies to shock and kill HIV-1 and thus represents a potential functional cure.
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