Identification of Five Interferon-Induced Cellular Proteins That Inhibit West Nile Virus and Dengue Virus Infections

被引：279

作者：

Jiang, Dong ^{[1
]}

Weidner, Jessica M. ^{[1
]}

Qing, Min ^{[2
]}

Pan, Xiao-Ben ^{[1
]}

Guo, Haitao ^{[1
]}

Xu, Chunxiao ^{[1
]}

Zhang, Xianchao ^{[1
]}

Birk, Alex ^{[3
]}

Chang, Jinhong ^{[1
]}

Shi, Pei-Yong ^{[2
]}

Block, Timothy M. ^{[1
,3
]}

Guo, Ju-Tao ^{[1
]}

机构：

[1] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Drexel Inst Biotechnol & Virol Res, Doylestown, PA 18902 USA

[2] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA

[3] Hepatitis B Fdn, Inst Hepatitis Virus Res, Doylestown, PA 18902 USA

来源：

JOURNAL OF VIROLOGY | 2010年 / 84卷 / 16期

基金：

美国国家卫生研究院;

关键词：

HEPATITIS-C VIRUS; INDUCIBLE GENE FAMILY; SINGLE-STRANDED RNA; ALPHA-INTERFERON; ANTIVIRAL RESPONSE; STIMULATED GENES; VIRAL SPREAD; REPLICATION; EXPRESSION; RESISTANCE;

D O I：

10.1128/JVI.02199-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Interferons (IFNs) are key mediators of the host innate antiviral immune response. To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically important flaviviruses, West Nile virus (WNV) and dengue virus (DENV), we tested 36 ISGs that are commonly induced by IFN-alpha for antiviral activity against the two viruses. We discovered that five ISGs efficiently suppressed WNV and/or DENV infection when they were individually expressed in HEK293 cells. Mechanistic analyses revealed that two structurally related cell plasma membrane proteins, IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection. In contrast, three IFN-induced cellular enzymes, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in viral proteins and/or RNA biosynthesis. Our results thus imply that the antiviral activity of IFN-alpha is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.

引用

页码：8332 / 8341

页数：10

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