IR@PKUHSC  > 北京大学基础医学院  > 病原生物学系
学科主题基础医学
Cell Culture-Adaptive Mutations Promote Viral Protein-Protein Interactions and Morphogenesis of Infectious Hepatitis C Virus
Jiang, Jieyun1; Luo, Guangxiang1,2
刊名JOURNAL OF VIROLOGY
2012-09-01
DOI10.1128/JVI.00004-12
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
WOS记录号WOS:000307627800006
项目编号AI091953 ; AI097318 ; AI092074 ; KSEF-148-502-10-272
资助机构NIH/NIAID ; Kentucky Science and Engineering Foundation
引用统计
被引频次:42[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52883
专题北京大学基础医学院_病原生物学系
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
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GB/T 7714
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.
APA Jiang, Jieyun,&Luo, Guangxiang.(2012).Cell Culture-Adaptive Mutations Promote Viral Protein-Protein Interactions and Morphogenesis of Infectious Hepatitis C Virus.JOURNAL OF VIROLOGY,86(17),8987-8997.
MLA Jiang, Jieyun,et al."Cell Culture-Adaptive Mutations Promote Viral Protein-Protein Interactions and Morphogenesis of Infectious Hepatitis C Virus".JOURNAL OF VIROLOGY 86.17(2012):8987-8997.
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