摘要: Human BST-2 inhibits HIV-1 replication by tethering nascent virions to the cell surface. HIV-1 codes Vpu that counteracts BST-2 by down-regulating this restriction factor from the cell surface. This important function makes Vpu a potential therapeutic target. Yet, no agents have been reported to block Vpu from antagonizing BST-2. In this study, we report a small molecule compound IMB-LA that abrogates the function of Vpu and thereby strongly suppresses HIV-1 replication by sensitizing the virus to BST-2 restriction. Further studies revealed that IMB-LA specifically inhibits Vpu-mediated degradation of BST-2 and restores the expression of BST-2 at the cell surface. Although IMB-LA does not prevent Vpu from interacting with BST-2 or beta-TrCP2-containing ubiquitin E3 ligase, sorting of BST-2 into lysosomes in Vpu-expressing cells is blocked by IMB-LA. Most importantly, HIV-1 release and infection is inhibited by IMB-LA only in BST-2-expressing cells. In summary, results herein demonstrated that IMB-LA could specifically inhibit the degradation of BST-2 induced by Vpu, and impair HIV-1 replication in a BST-2 dependent manner, suggesting the feasibility of utilizing small molecule compounds to disable the antagonist function of Vpu and thereby expose HIV-1 to the restriction by BST-2.
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期刊:
SCIENTIFIC REPORTS
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分类:
生物学
>>
生物物理学
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引用:
ChinaXiv:201605.01309
(或此版本
ChinaXiv:201605.01309V1)
DOI:10.12074/201605.01309V1
CSTR:32003.36.ChinaXiv.201605.01309.V1
- 推荐引用方式:
Mi, Zeyun,Ding, Jiwei,Zhang, Quan,Ma, Ling,Shan, Guangzhi,Li, Xiaoyu,Zhou, Jinming,Cen, Shan,Mi, Zeyun,Ding, Jiwei,Zhang, Quan,Ma, Ling,Shan, Guangzhi,Li, Xiaoyu,Zhou, Jinming,Cen, Shan,Zhao, Jianyuan,Wei, Tao,Liu, Zhenlong,Liang, Chen,Guo, Fei,Mi, Zeyun,Yu, Haisheng,Zhang, Liguo.(2016).A small molecule compound IMB-LA inhibits HIV-1 infection by preventing viral Vpu from antagonizing the host restriction factor BST-2.中国科学院科技论文预发布平台.[ChinaXiv:201605.01309]
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