Blight K J, Kolykhalov A A, Rice C M
Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110-1093, USA.
Science. 2000 Dec 8;290(5498):1972-4. doi: 10.1126/science.290.5498.1972.
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.
丙型肝炎病毒（HCV）感染是一个全球性的健康问题，全球估计有1.7亿人受到影响。我们报告了在HCV非结构蛋白NS5A中发现的多个独立适应性突变，这些突变在体外具有增强的复制能力。在这些适应性突变中，有一个单氨基酸取代，使HCV RNA能在10%的转染肝癌细胞中复制，还有一个47个氨基酸的缺失，该缺失区域包含干扰素（IFN）敏感性决定区（ISDR）。与ISDR无关，干扰素-α在体外能迅速抑制HCV RNA复制。这项工作建立了一个强大的基于细胞的系统，用于HCV复制的遗传和功能分析。
