Activation of HIV-1 expression in latently infected CD4+T cells by the small molecule PKC412

作者：Ao, Zhujun; Zhu, Rong; Tan, Xiaoli; Liu, Lisa; Chen, Liyu; Liu, Shuiping; Yao, XiaoJian^*

来源：Virology Journal, 2016, 13(1): 177.

DOI：10.1186/s12985-016-0637-9

• HIV latency
• PKC412
• NF-kappa B signaling
• ACH2 cells
• Resting CD4+T cells

Background: HIV-1 latency is a major obstacle for HIV-1 eradication. Extensive efforts are being directed toward the reactivation of latent HIV reservoirs with the aim of eliminating latently infected cells via the host immune system and/or virus-mediated cell lysis.
Results: We screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412 (midostaurin, a broad-spectrum kinase inhibitor), can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4+ T cells. PKC412 reactivated HIV-1 expression in ACH2 cells in a dose-and time-dependent manner. Our results also suggest that the nuclear factor kappa B (NF-kappa B) signaling could be one of cellular pathways activated during PKC412-mediated activation of latent HIV-1 expression. Additionally, combining PKC412 with the HDAC inhibitor vorinostat (VOR) had an additive effect on HIV-1 reactivation in both ACH2 cells and infected resting CD4+ T cells.
Conclusions: These studies provide evidence that PKC412 is a new compound with the potential for optimization as a latency-reactivator to eradicate HIV-1 infection.

• 出版日期2016-10-21
• 单位中南大学