Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146–152, 2017.
Bibliographical noteFunding Information:
We thank Dr. Charles Rice for Huh7.5 cells and 9E10 antibody, and Dr. Takaji Wakita for JFH1 cell culture-infectious clone. Most of cDNA clones for genotype 1a HCV were kindly provided by Dr. Stanley Lemon.
All Science Journal Classification (ASJC) codes
- Infectious Diseases