Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui.

Content Provider	Europe PMC
Author	Wang, Pengfei Lu, Panpan Qu, Xiying Shen, Yinzhong Zeng, Hanxian Zhu, Xiaoli Zhu, Yuqi Li, Xian Wu, Hao Xu, Jianqing Lu, Hongzhou Ma, Zhongjun Zhu, Huanzhang
Abstract	Cells harboring latent HIV-1 pose a major obstacle to eradication of the virus. The 'shock and kill' strategy has been broadly explored to purge the latent reservoir; however, none of the current latency-reversing agents (LRAs) can safely and effectively activate the latent virus in patients. In this study, we report an ingenol derivative called EK-16A, isolated from the traditional Chinese medicinal herb Euphorbia kansui, which displays great potential in reactivating latent HIV-1. A comparison of the doses used to measure the potency indicated EK-16A to be 200-fold more potent than prostratin in reactivating HIV-1 from latently infected cell lines. EK-16A also outperformed prostratin in ex vivo studies on cells from HIV-1-infected individuals, while maintaining minimal cytotoxicity effects on cell viability and T cell activation. Furthermore, EK-16A exhibited synergy with other LRAs in reactivating latent HIV-1. Mechanistic studies indicated EK-16A to be a PKCγ activator, which promoted both HIV-1 transcription initiation by NF-κB and elongation by P-TEFb signal pathways. Further investigations aimed to add this compound to the therapeutic arsenal for HIV-1 eradication are in the pipeline.
Journal	Scientific Reports [Sci Rep]
Volume Number	7
DOI	10.1038/s41598-017-07157-0
PubMed Central reference number	PMC5573388
Issue Number	1
PubMed reference number	28842560
e-ISSN	20452322
Language	English
Publisher	Nature Publishing Group
Publisher Date	2017-08-25
Publisher Place	London
Access Restriction	Open
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary