2. Academic Validation
  3. The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells

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

  • Oncotarget. 2017 Oct 6;8(55):94104-94116. doi: 10.18632/oncotarget.21585.
Hanyu Pan 1,  Panpan Lu 1,  Yinzhong Shen 2,  Yanan Wang 1,  Zhengtao Jiang 1,  Xinyi Yang 1,  Yangcheng Zhong 1,  He Yang 1,  Inam Ulla Khan 1,  Muya Zhou 1,  Bokang Li 1,  Ziyu Zhang 1,  Jianqing Xu 2,  Hongzhou Lu 2,  Huanzhang Zhu 1
Affiliations

Affiliations

  • 1 State 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.
  • 2 Department of Infectious Diseases and Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
PMID: 29212213 DOI: 10.18632/oncotarget.21585
Abstract

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.

Keywords

BET inhibitor; CDK9 T-loop; HIV-1 latency; bromosporine; reactivation.

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