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

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dc.contributor.authorAo, Zhujun
dc.contributor.authorZhu, Rong
dc.contributor.authorTan, Xiaoli
dc.contributor.authorLiu, Lisa
dc.contributor.authorChen, Liyu
dc.contributor.authorLiu, Shuiping
dc.contributor.authorYao, XiaoJian
dc.date.accessioned2016-10-21T13:59:28Z
dc.date.available2016-10-21T13:59:28Z
dc.date.issued2016-10-21
dc.date.updated2016-10-21T06:03:09Z
dc.description.abstractAbstract 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.
dc.identifier.citationVirology Journal. 2016 Oct 21;13(1):177
dc.identifier.urihttp://dx.doi.org/10.1186/s12985-016-0637-9
dc.identifier.urihttp://hdl.handle.net/1993/31897
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderThe Author(s).
dc.titleActivation of HIV-1 expression in latently infected CD4+ T cells by the small molecule PKC412
dc.typeJournal Article
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