Efficient initiation of HCV RNA replication in cell culture
Efficient initiation of HCV RNA replication in cell culture
复制标题
DOI：
10.1126/science.290.5498.1972
复制
发表时间：
2000-12-08
期刊：
影响因子：
56.9
通讯作者：
Rice, CM
中科院分区：
文献类型：
--
作者：
Blight, KJ;Kolykhalov, AA;Rice, CM
丙型肝炎病毒（HCV）感染是一个全球性的健康问题，影响全球估计1.7亿人。我们报告了在HCV非结构蛋白NS 5A中聚集的多个独立适应性突变的鉴定，并在体外赋予增加的复制能力。在这些适应性突变是一个单一的氨基酸取代，允许HCV RNA复制在10%的转染肝癌细胞和删除47个氨基酸，包括干扰素（IFN）敏感性决定区（ISDR）。独立的ISDR，IFN-α在体外迅速抑制HCV RNA复制。这项工作建立了一个强大的，基于细胞的系统，HCV复制的遗传和功能分析。
Hepatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. We report the identification of multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro. Among these adaptive mutations were a single amino acid substitution that allowed HCV RNA replication in 10% of transfected hepatoma cells and a deletion of 47 amino acids encompassing the interferon (IFN) sensitivity determining region (ISDR). Independent of the ISDR, IFN-alpha rapidly inhibited HCV RNA replication in vitro. This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication.