title: Genetic variability and diversity of intracellular genome-length hepatitis C virus RNA in long-term cell culture.
abstract: Hepatitis C virus (HCV) is known to circulate persistently in vivo as a complex population of different but closely related viral variants. To understand the quasispecies nature of HCV, we performed genetic analysis of intracellular HCV RNAs obtained in long-term cell culture of genome-length HCV-RNA-replicating cells. The results revealed that genetic mutations in HCV RNAs accumulated in a time-dependent manner, and that the mutation rates of HCV RNAs were 3.5-4.8 x 10(-3) base substitutions/site/year. The mutation rates of nonstructural regions that are essential for RNA replication were lower than those of structural regions. The genetic diversity of HCVs was also enlarged in a time-dependent manner. Furthermore, we found that the GC content of HCV RNA was increased in a time-dependent manner. These results suggest that an HCV-RNA-replicating cell culture system would be useful for analysis of the evolutionary dynamics and variations of HCV.
authors.affiliation: Department of Tumor Virology, Okayama University of Graduate School of Medicine, Okayama, Japan. nkato@md.okayama-u.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Ariumi
authors.forename: H
authors.initials: H
authors.lastname: Dansako
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics* / Q000254:growth & development*; D006801:Humans; D009154:Mutation / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics*; D013997:Time Factors; D014779:Virus Replication / Q000235:genetics* / Q000502:physiology
chemical_list: D012367:RNA, Viral