The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells

• Published in: Oncotarget 2017-11, Vol.8 (55), p.94104-94116
• Main Authors: Pan, Hanyu, Lu, Panpan, Shen, Yinzhong, Wang, Yanan, Jiang, Zhengtao, Yang, Xinyi, Zhong, Yangcheng, Yang, He, Khan, Inam Ulla, Zhou, Muya, Li, Bokang, Zhang, Ziyu, Xu, Jianqing, Lu, Hongzhou, Zhu, Huanzhang
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.21585

The long-lived latent HIV-1 reservoir is the major barrier for complete cure of Acquired Immune Deficiency Syndrome (AIDS). Here we report that a novel bromodomain and extraterminal domain (BET) inhibitor bromosporine which can broadly target BETs, is able to potently reactivate HIV-1 replication in different latency models alone and more powerful when combined with prostratin or TNF-α. Furthermore, the treatment with bromosporine induced HIV-1 full-length transcripts in resting CD4+ T cells from infected individuals with suppressive antiretroviral therapy (ART) , with no obvious cytotoxicity or global activation of T cell. Finally, our data suggest that Tat plays a critical role in the bromosporine-mediated reactivation of latent HIV-1, which involved the increase of CDK9 T-loop phosphorylation. In summary, we found that the BET inhibitor bromosporine, alone or with other activators, might be a candidate for future HIV-1 eradication strategies.