Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation

	Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation
	Zhu YP 1,2; Chen GF 1; Lv FX 1; Wang XL 1; Ji X 1; Xu YH 1; Sun J 1; Wu L 3; Zheng YT 4; Gao GX*1; gaogx@moon.ibp.ac.cn
	2011
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷号	108 期号:38 页码:15834-15839
合作性质	其它
摘要	The zinc-finger antiviral protein (ZAP) was originally identified as a host factor that inhibits the replication of Moloney murine leukemia virus. Here we report that ZAP inhibits HIV-1 infection by promoting the degradation of specific viral mRNAs. Overexpression of ZAP rendered cells resistant to HIV-1 infection in a ZAP expression level-dependent manner, whereas depletion of endogenous ZAP enhanced HIV-1 infection. Both human and rat ZAP inhibited the propagation of replication-competent HIV-1. ZAP specifically targeted the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. We provide evidence indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA exosome to degrade the RNA body from the 3' end. In addition, ZAP recruits cellular decapping complex through its cofactor RNA helicase p72 to initiate degradation of the target viral mRNA from the 5' end. Depletion of each of these mRNA degradation enzymes reduced ZAP's activity. Our results indicate that ZAP inhibits HIV-1 by recruiting both the 5' and 3' mRNA degradation machinery to specifically promote the degradation of multiply spliced HIV-1 mRNAs.
关键词	Retrovirus Host Restriction Factor Rna Degradation
资助者	This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.). ; This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.). ; This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.). ; This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.).
收录类别	SCI
语种	英语
资助者	This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.). ; This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.). ; This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.). ; This work was supported in part by National Science Foundation Grants 30530020 and 81028011, Ministry of Science and Technology 973 Program Grant 2006CB504302, and Ministry of Health of China Grant 2009ZX09501-029 (to G.G.); and by National Science Foundation Grant 30800053 and Ministry of Health of China Grant 2008ZX10001-002 (to G.C.).
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/353002/6815
专题	科研部门_分子免疫药理学（郑永唐）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	gaogx@moon.ibp.ac.cn
作者单位	1.Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China 2.Graduate School of the Chinese Academy of Sciences, Beijing 100049, China 3.Center for Retrovirus Research, Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210 4.Key Laboratory of Animal Models and Human Disease, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
推荐引用方式 GB/T 7714	Zhu YP,Chen GF,Lv FX,et al. Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2011,108(38):15834-15839.
APA	Zhu YP.,Chen GF.,Lv FX.,Wang XL.,Ji X.,...&gaogx@moon.ibp.ac.cn.(2011).Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,108(38),15834-15839.
MLA	Zhu YP,et al."Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108.38(2011):15834-15839.

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