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学科主题: 基础医学
题名:
Cell Culture-Adaptive Mutations Promote Viral Protein-Protein Interactions and Morphogenesis of Infectious Hepatitis C Virus
作者: Jiang, Jieyun1; Luo, Guangxiang1,2
刊名: JOURNAL OF VIROLOGY
发表日期: 2012-09-01
DOI: 10.1128/JVI.00004-12
卷: 86, 期:17, 页:8987-8997
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Virology
研究领域[WOS]: Virology
关键词[WOS]: CORE PROTEIN ; NONSTRUCTURAL PROTEINS ; COMPENSATORY MUTATIONS ; REPLICATION COMPLEX ; ROBUST PRODUCTION ; APOLIPOPROTEIN-E ; RNA REPLICATION ; NS5A ; GENOME ; DOMAIN
英文摘要:

Recent genetic studies suggested that viral nonstructural (NS) proteins play important roles in morphogenesis of flaviviruses, particularly hepatitis C virus (HCV). Adaptive and compensatory mutations occurring in different NS proteins were demonstrated to promote HCV production in cell culture. However, the underlying molecular mechanism of NS proteins in HCV morphogenesis is poorly understood. We have isolated a cell culture-adapted HCV of genotype 2a (JFHI) which grew to an infectious titer 3 orders of magnitude higher than that of wild-type virus. Sequence analysis identified a total of 16 amino acid mutations in core (C), El, NS2, NS3, NS5A, and NS5B, with the majority of mutations clustered in NS5A. Reverse genetic analysis of these mutations individually or in different combinations demonstrated that amino acid mutations in NS2 and NS5A markedly enhanced HCV production. Additionally, mutations in C, El, NS3, and NS5B synergistically promoted HCV production in the background of NS2 and NS5A mutations. Adaptive mutations in NS5A domains I, II, and III independently enhanced HCV production, suggesting that all three domains of NS5A are important for HCV morphogenesis. More importantly, adaptive mutations greatly enhanced physical interactions among HCV structural and NS proteins, as determined by studies with coimmunoprecipitation and mammalian two-hybrid assays. Collectively, these findings demonstrate that adaptive mutations can enhance specific protein-protein interactions among viral structural and NS proteins and therefore promote the assembly of infectious HCV particles.

语种: 英语
所属项目编号: AI091953 ; AI097318 ; AI092074 ; KSEF-148-502-10-272
项目资助者: NIH/NIAID ; Kentucky Science and Engineering Foundation
WOS记录号: WOS:000307627800006
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52883
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA
2.Peking Univ, Coll Basic Med Sci, Dept Microbiol, Beijing 100871, Peoples R China

Recommended Citation:
Jiang, Jieyun,Luo, Guangxiang. Cell Culture-Adaptive Mutations Promote Viral Protein-Protein Interactions and Morphogenesis of Infectious Hepatitis C Virus[J]. JOURNAL OF VIROLOGY,2012,86(17):8987-8997.
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