Identification of specific regions in hepatitis C virus core, NS 2 and NS 5 A that genetically interact with p7 and co‐ordinate infectious virus production

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 JFH 1 chimeric viruses encoding the partial or full‐length p7 protein of the HCV ‐A strain of genotype 1b ( GT 1b; Virology ; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild‐type JFH 1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core ( K 74 M ), NS 2 ( T 23 N , H 99 P ) and NS 5A ( D 251 G ). 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, NS 2 and NS 5 A . In addition, it was demonstrated that the NS 2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT 6 of HCV .