A novel bromodomain inhibitor, CPI-203, serves as an HIV-1 latency-reversing agent by activating positive transcription elongation factor b.
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.
['Liang|Taizhen|T|', 'Zhang|Xuanxuan|X|', 'Lai|Fangyuan|F|', 'Lin|Jian|J|', 'Zhou|Chenliang|C|', 'Xu|Xinfeng|X|', 'Tan|Xinghua|X|', 'Liu|Shuwen|S|', 'Li|Lin|L|']
D000081:Acetamides D000328:Adult D000818:Animals D001381:Azepines D015496:CD4-Positive T-Lymphocytes D005260:Female D015497:HIV-1 D006801:Humans D019169:Jurkat Cells D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008875:Middle Aged D042925:Positive Transcriptional Elongation Factor B D000072417:Protein Domains D014775:Virus Activation D017735:Virus Latency
CPI-203 Latency-reversing agent Shock and kill Latent HIV-1 p-TEFb