Interferon-Inducible Cholesterol-25-Hydroxylase Inhibits Hepatitis C Virus Replication via Distinct Mechanisms

被引：81

作者：

Chen, Yongzhi ^{[1
,2
]}

Wang, Shanshan

Yi, Zhaohong ^{[1
]}

Tian, Huabin ^{[1
,2
]}

Aliyari, Roghiyh ^{[3
]}

Li, Yanhua ^{[7
]}

Chen, Gang ^{[7
]}

Liu, Ping ^{[1
]}

Zhong, Jin ^{[8
]}

Chen, Xinwen ^{[9
]}

Du, Peishuang ^{[1
]}

Su, Lishan ^{[1
,4
,5
]}

Qin, F. Xiao-Feng ^{[6
]}

Deng, Hongyu ^{[1
]}

Cheng, Genhong ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100080, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[4] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[7] CAAS, Inst Qual Standard & Testing Technol Agroproduct, Beijing, Peoples R China

[8] Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China

[9] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Peoples R China

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

DENSITY-LIPOPROTEIN RECEPTOR; NONSTRUCTURAL PROTEIN; CHOLESTEROL; IDENTIFICATION; BINDING; NS5A; 25-HYDROXYCHOLESTEROL; TARGET; IFITM1;

D O I：

10.1038/srep07242

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cholesterol 25-hydroxylase (CH25H) as an interferon-stimulated gene (ISG) has recently been shown to exert broad antiviral activity through the production of 25-hydroxycholesterol (25HC), which is believed to inhibit the virus-cell membrane fusion during viral entry. However, little is known about the function of CH25H on HCV infection and replication and whether antiviral function of CH25H is exclusively mediated by 25HC. In the present study, we have found that although 25HC produced by CH25H can inhibit HCV replication, CH25H mutants lacking the hydroxylase activity still carry the antiviral activity against HCV but not other viruses such as MHV-68. Further studies have revealed that CH25H can interact with the NS5A protein of HCV and inhibit its dimer formation, which is essential for HCV replication. Thus, our work has uncovered a novel mechanism by which CH25H restricts HCV replication, suggesting that CH25H inhibits viral infection through both 25HC-dependent and independent events.

引用

页数：8

共 41 条

[1] Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and insigs [J].