Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections
Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections
复制标题
新型巨大戟二萜醇衍生物对急性和潜伏 HIV-1 感染的双重作用
DOI：
10.1016/j.antiviral.2019.104555
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发表时间：
2019
影响因子：
7.6
通讯作者：
Zhu Huanzhang
中科院分区：
文献类型：
--
作者：
Yang He;Li Xian;Yang Xinyi;Lu Panpan;Wang Yanan;Jiang Zhengtao;Pan Hanyu;Zhao Lin;Zhu Yuqi;Khan Inam Ullah;Shen Yinzhong;Lu Hongzhou;Zhang Tong;Jiang Guochun;Ma Zhongjun;Wu Hao;Zhu Huanzhang
The latent reservoir of HIV-1 in resting memory CD4+T cells serves as a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 is proposed as a promising strategy for the clearance of the viral reservoirs. Because of the limitations of current latency reversal agents (LRAs), identification of new LRAs is urgently required. Here, we analyzed Euphorbia kansui extracts and obtained three ingenol derivative compounds named EK-1A, EK-5A and EK-15A. We found that ingenol derivatives can effectively reactivate latent HIV-1 at very low (nanomolar) concentrations in HIV latency modelin vitro. Furthermore, ingenol derivatives exhibited synergy with other LRAs in reactivating latent HIV-1. We verified that EK-15A can promote latent HIV-1 reactivation in theex vivoresting CD4+T cells isolated from the peripheral blood of HIV-infected individuals on suppressive antiretroviral therapy. In addition, ingenol derivatives down-regulated the expression of cell surface HIV co-receptors CCR5 and CXCR4, therefore potentially preventing new infection of HIV-1. Our results indicated that the ingenol derivatives extracted from Euphorbia kansui have dual functions: reactivation of latent HIV-1 and inhibition of HIV-1 infection.
