Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production

Summary 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; 2...

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Bibliographic Details
Published in:Journal of viral hepatitis 2013-04, Vol.20 (4), p.e66-e71
Main Authors: Gouklani, H., Beyer, C., Drummer, H., Gowans, E. J., Netter, H. J., Haqshenas, G.
Format: Article
Language:English
Subjects:
Amino acid substitution
core
DNA Mutational Analysis
Hepacivirus - genetics
Hepacivirus - physiology
Hepatitis
Hepatitis C virus
JFH1
morphogenesis
NS2
NS5A
Protein Interaction Domains and Motifs
Protein Interaction Mapping
Proteins
Viral Core Proteins - genetics
Viral Core Proteins - metabolism
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Viral Proteins - genetics
Viral Proteins - metabolism
Virus Replication
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Summary:Summary 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.
ISSN:1352-0504
1365-2893
DOI:10.1111/jvh.12004