TY - JOUR
T1 - Genetic variability and diversity of intracellular genome-length hepatitis C virus RNA in long-term cell culture
AU - Kato, Nobuyuki
AU - Abe, K.
AU - Mori, K.
AU - Ariumi, Y.
AU - Dansako, H.
AU - Ikeda, Masanori
N1 - Funding Information:
We thank T. Nakamura for his technical assistance. This work was supported by a grant-in-aid for the third-term comprehensive 10-year strategy for cancer control and by a grant-in-aid for research on hepatitis, both from the Ministry of Health, Labor, and Welfare of Japan.
PY - 2009/1
Y1 - 2009/1
N2 - 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 × 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.
AB - 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 × 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.
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U2 - 10.1007/s00705-008-0282-8
DO - 10.1007/s00705-008-0282-8
M3 - Article
C2 - 19082684
AN - SCOPUS:58149316016
VL - 154
SP - 77
EP - 85
JO - Archives of Virology
JF - Archives of Virology
SN - 0304-8608
IS - 1
ER -
