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Hepatitis C Virus Nonstructural Protein 5B Is Involved in Virus Morphogenesis
- Source :
- Journal of Virology. 86:5080-5088
- Publication Year :
- 2012
- Publisher :
- American Society for Microbiology, 2012.
-
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.
- Subjects :
- Models, Molecular
Genotype
Protein Conformation
viruses
Hepatitis C virus
Molecular Sequence Data
Immunology
Genome, Viral
Hepacivirus
Viral Nonstructural Proteins
Biology
Virus Replication
medicine.disease_cause
Microbiology
Catalysis
Virus
Cell Line
Viral Proteins
chemistry.chemical_compound
Virology
medicine
Humans
Amino Acid Sequence
NS5B
Mutation
Structure and Assembly
Virus Assembly
virus diseases
biochemical phenomena, metabolism, and nutrition
Molecular biology
digestive system diseases
NS2-3 protease
Protein Transport
Amino Acid Substitution
Viral replication
chemistry
Virion assembly
Insect Science
RNA, Viral
Viral genome replication
Protein Binding
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....3e160d6ea18929a170c236a5d469aee2