Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/88363
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Type: Journal article
Title: Hepatitis C virus nonstructural protein 5B is involved in virus morphogenesis
Author: Gouklani, H.
Bull, R.
Beyer, C.
Coulibaly, F.
Gowans, E.
Drummer, H.
Netter, H.
White, P.
Haqshenas, G.
Citation: Journal of Virology, 2012; 86(9):5080-5088
Publisher: American Society for Microbiology
Issue Date: 2012
ISSN: 0022-538X
1098-5514
Statement of
Responsibility: 
Hamed Gouklani, Rowena A. Bull, Claudia Beyer, Fasséli Coulibaly, Eric J. Gowans, Heidi E. Drummer, Hans J. Netter, Peter A. White and Gholamreza Haqshenas
Abstract: The p7 protein of hepatitis C virus (HCV) is a viroporin that is dispensable for viral genome replication but plays a critical role in virus morphogenesis. In this study, we generated a JFH1-based intergenotypic chimeric genome that encoded a heterologous genotype 1b (GT1b) p7. The parental intergenotypic chimeric genome was nonviable in human hepatoma cells, and infectious chimeric virions were produced only when cells transfected with the chimeric genomes were passaged several times. Sequence analysis of the entire polyprotein-coding region of the recovered chimeric virus revealed one predominant amino acid substitution in nonstructural protein 2 (NS2), T23N, and one in NS5B, K151R. Forward genetic analysis demonstrated that each of these mutations per se restored the infectivity of the parental chimeric genome, suggesting that interactions between p7, NS2, and NS5B were required for virion assembly/maturation. p7 and NS5B colocalized in cellular compartments, and the NS5B mutation did not affect the colocalization pattern. The NS5B K151R mutation neither increased viral RNA replication in human hepatoma cells nor altered the polymerase activity of NS5B in an in vitro assay. In conclusion, this study suggests that HCV NS5B is involved in virus morphogenesis.
Keywords: Cell Line
Humans
Hepacivirus
Viral Proteins
Viral Nonstructural Proteins
RNA, Viral
Amino Acid Substitution
Virus Replication
Virus Assembly
Amino Acid Sequence
Protein Conformation
Protein Binding
Protein Transport
Genotype
Mutation
Genome, Viral
Catalysis
Models, Molecular
Molecular Sequence Data
Rights: Copyright © 2012 by the American Society for Microbiology.
DOI: 10.1128/JVI.07089-11
Appears in Collections:Aurora harvest 2
Microbiology and Immunology publications

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