Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Scientific reports, 2017-08, Vol.7 (1), p.9451-15, Article 9451

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.