Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1

被引:286
作者
Herker, Eva [1 ,2 ,3 ]
Harris, Charles [2 ,3 ,4 ]
Hernandez, Celine [5 ]
Carpentier, Arnaud [5 ]
Kaehlcke, Katrin [1 ]
Rosenberg, Arielle R. [5 ]
Farese, Robert V., Jr. [2 ,3 ,4 ,6 ]
Ott, Melanie [1 ,2 ,3 ]
机构
[1] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[4] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA
[5] Univ Paris 05, EA Virol Hepatite C 4474, Paris, France
[6] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
基金
美国国家卫生研究院;
关键词
LIPID DROPLETS; CORE PROTEIN; CELL-CULTURE; VIRAL GENOME; REPLICATION; LOCALIZATION; SECRETION; DGAT; MICE;
D O I
10.1038/nm.2238
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Hepatitis C virus (HCV) infection is closely tied to the lipid metabolism of liver cells. Here we identify the triglyceride-synthesizing enzyme diacylglycerol acyltransferase-1 (DGAT1) as a key host factor for HCV infection. DGAT1 interacts with the viral nucleocapsid core and is required for the trafficking of core to lipid droplets. Inhibition of DGAT1 activity or RNAi-mediated knockdown of DGAT1 severely impairs infectious virion production, implicating DGAT1 as a new target for antiviral therapy.
引用
收藏
页码:1295 / 1298
页数:4
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