Kato Nobuyuki, Abe K, Mori K, Ariumi Y, Dansako H, Ikeda M
Department of Tumor Virology, Okayama University of Graduate School of Medicine, Okayama, Japan.
Arch Virol. 2009;154(1):77-85. doi: 10.1007/s00705-008-0282-8. Epub 2008 Dec 10.
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.
已知丙型肝炎病毒（HCV）在体内以不同但密切相关的病毒变体的复杂群体形式持续循环。为了了解HCV的准种性质，我们对从基因组长度HCV - RNA复制细胞的长期细胞培养中获得的细胞内HCV RNA进行了基因分析。结果显示，HCV RNA中的基因突变以时间依赖性方式积累，并且HCV RNA的突变率为3.5 - 4.8×10（-3）碱基替换/位点/年。RNA复制所必需的非结构区域的突变率低于结构区域的突变率。HCV的遗传多样性也以时间依赖性方式扩大。此外，我们发现HCV RNA的GC含量以时间依赖性方式增加。这些结果表明，HCV - RNA复制细胞培养系统将有助于分析HCV的进化动力学和变异。
