The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells
Metrics: PDF 916 views | HTML 1587 views | ?
Hanyu Pan1,*, Panpan Lu1,*, Yinzhong Shen2, Yanan Wang1, Zhengtao Jiang1, Xinyi Yang1, Yangcheng Zhong1, He Yang1, Inam Ulla Khan1, Muya Zhou1, Bokang Li1, Ziyu Zhang1, Jianqing Xu2, Hongzhou Lu2 and Huanzhang Zhu1
1State Key Laboratory of Genetic Engineering and Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, School of Life Sciences, Fudan University, Shanghai, China
2Department of Infectious Diseases and Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
*These authors have contributed equally to this work
Huanzhang Zhu, email: email@example.com
Keywords: bromosporine, HIV-1 latency, reactivation, BET inhibitor, CDK9 T-loop
Received: July 12, 2017 Accepted: September 21, 2017 Published: October 06, 2017
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) ex vivo, 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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.