title: Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production.
abstract: 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.
authors.affiliation: The Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Vic, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Gouklani
authors.forename: C
authors.initials: C
authors.lastname: Beyer
authors.forename: H
authors.initials: H
authors.lastname: Drummer
authors.forename: E J
authors.initials: EJ
authors.lastname: Gowans
authors.forename: H J
authors.initials: HJ
authors.lastname: Netter
authors.forename: G
authors.initials: G
authors.lastname: Haqshenas
mesh_terms: D004252:DNA Mutational Analysis; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D000086082:Viroporin Proteins; D012324:RNA-Dependent RNA Polymerase
chemical_list: D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C097010:NS2 protein, Hepatitis C virus; C069130:nucleocapsid protein, Hepatitis C virus; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase