Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd, Xuhui District, Shanghai 200032, China.
Shenzhen Nanshan People's Hospital of Shenzhen University, Shenzhen 518052, China.
Microbes Infect. 2018 Oct-Nov;20(9-10):626-634. doi: 10.1016/j.micinf.2017.10.003. Epub 2017 Nov 8.
Although combination antiretroviral therapy (cART) is highly effective in suppressing human immunodeficiency virus type 1 (HIV-1) replication, it fails to eradicate the virus from HIV-1-infected individuals because HIV-1 integrates into the resting CD4 T cells, establishing latently infected reservoirs. Histone deacetylation is a key element in regulating HIV-1 latent infection. Chidamide, a new anticancer drug, is a novel type of selective histone deacetylase inhibitor. Here we showed that chidamide effectively reactivated HIV-1 latent provirus in different latently infected cell lines in a dose- and time-dependent manner. Chidamide had relatively low cytotoxicity to peripheral blood mononuclear cells (PBMCs) and other latent cell lines. We have demonstrated that chidamide reactivated HIV-1 latent provirus through the NF-κB signaling pathway. The replication of the newly reactivated HIV-1 could then be effectively inhibited by the anti-HIV-1 drugs Zidovudine, Nevirapine, and Indinavir. Therefore, chidamide might be used in combination with cART for functional HIV-1 cure.
尽管联合抗逆转录病毒疗法（cART）在抑制人类免疫缺陷病毒 1 型（HIV-1）复制方面非常有效，但它无法从感染 HIV-1 的个体中彻底清除病毒，因为 HIV-1 整合到静止的 CD4 T 细胞中，建立潜伏感染的储库。组蛋白去乙酰化是调节 HIV-1 潜伏感染的关键因素。Chidamide 是一种新型抗癌药物，是一种新型选择性组蛋白去乙酰化酶抑制剂。在这里，我们显示 Chidamide 以剂量和时间依赖的方式有效地重新激活了不同潜伏感染细胞系中的 HIV-1 潜伏前病毒。Chidamide 对外周血单核细胞（PBMC）和其他潜伏细胞系的细胞毒性相对较低。我们已经证明，Chidamide 通过 NF-κB 信号通路重新激活 HIV-1 潜伏前病毒。新重新激活的 HIV-1 的复制可以通过抗 HIV-1 药物齐多夫定、奈韦拉平、和茚地那韦有效地抑制。因此，Chidamide 可能与 cART 联合用于功能性 HIV-1 治愈。
