Genetic variability and diversity of intracellular genome-length hepatitis C virus RNA in long-term cell culture.
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.
Kato
Nobuyuki
N
Department of Tumor Virology, Okayama University of Graduate School of Medicine, Okayama, Japan. nkato@md.okayama-u.ac.jp
Abe
K
K
Mori
K
K
Ariumi
Y
Y
Dansako
H
H
Ikeda
M
M
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
D012367:RNA, Viral