Title |
Activation of HIV-1 expression in latently infected CD4+ T cells by the small molecule PKC412
|
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Published in |
Virology Journal, October 2016
|
DOI | 10.1186/s12985-016-0637-9 |
Pubmed ID | |
Authors |
Zhujun Ao, Rong Zhu, Xiaoli Tan, Lisa Liu, Liyu Chen, Shuiping Liu, XiaoJian Yao |
Abstract |
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. 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. These studies provide evidence that PKC412 is a new compound with the potential for optimization as a latency-reactivator to eradicate HIV-1 infection. |
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Geographical breakdown
Country | Count | As % |
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United States | 1 | 20% |
Unknown | 4 | 80% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 60% |
Science communicators (journalists, bloggers, editors) | 2 | 40% |
Mendeley readers
Geographical breakdown
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Unknown | 20 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 6 | 30% |
Researcher | 3 | 15% |
Student > Ph. D. Student | 3 | 15% |
Student > Bachelor | 2 | 10% |
Student > Doctoral Student | 1 | 5% |
Other | 2 | 10% |
Unknown | 3 | 15% |
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Immunology and Microbiology | 2 | 10% |
Medicine and Dentistry | 2 | 10% |
Other | 4 | 20% |
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