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Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production
被引:13
作者:
Gouklani, H.
[1
,2
]
Beyer, C.
[1
]
Drummer, H.
[1
,2
]
Gowans, E. J.
[1
]
Netter, H. J.
[2
]
Haqshenas, G.
[1
,2
]
机构:
[1] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia
[2] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia
基金:
英国医学研究理事会;
关键词:
core;
JFH1;
morphogenesis;
NS2;
NS5A;
p7;
NONSTRUCTURAL PROTEIN 5A;
RNA REPLICATION;
ION-CHANNEL;
MEMBRANE ASSOCIATION;
DOMAIN-III;
FORMS;
D O I:
10.1111/jvh.12004
中图分类号:
R57 [消化系及腹部疾病];
学科分类号:
摘要:
The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full-length p7 protein of the HCV-A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild-type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV.
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页码:e66 / e71
页数:6
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