title: Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes.
abstract: 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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Aeri
authors.initials: A
authors.lastname: Chung
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Jin
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ahnsh@yuhs.ac.|Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. ahnsh@yuhs.ac.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. kimst@yuhs.ac.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. kimst@yuhs.ac.
authors.forename: Seungtaek
authors.initials: S
authors.lastname: Kim
mesh_terms: D000220:Adaptation, Biological; D002460:Cell Line; D004252:DNA Mutational Analysis; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014776:Virus Cultivation; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
chemical_list: D050505:Mutant Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: NS5A; cell culture-adaptive mutation; genotype; hepatitis C virus