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- Title
Activation of HIV-1 expression in latently infected CD4+ T cells by the small molecule PKC412.
- Authors
Zhujun Ao; Rong Zhu; Xiaoli Tan; Lisa Liu; Liyu Chen; Shuiping Liu; XiaoJian Yao
- Abstract
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 κB (NF-κB) 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.
- Subjects
HIV infections; CD4 antigen; T cells; SMALL molecules; GENE expression
- Publication
Virology Journal, 2016, Vol 13, Issue 1, p1
- ISSN
1743-422X
- Publication type
Article
- DOI
10.1186/s12985-016-0637-9