Genotypic& phenotypic characterization of the HCV polymerase (NS5B) in HIV

描述（由申请人提供）：丙型肝炎病毒（HCV）合并感染已成为艾滋病毒/艾滋病感染者发病和死亡的主要原因。流行病学研究清楚地表明，HIV/HCV合并感染与HCV复制增强、纤维化增加和肝脏疾病的发展相关。HIV还增加了HCV结构基因的准物种多样性。然而，与结构基因组区域相比，HCV基因组的非结构区域（如NS5B）受到不同的选择压力——纯化选择对于保持病毒复制、耐药突变和/或代偿突变至关重要的酶功能是必要的。尽管NS5B作为HCV治疗的新兴靶点越来越重要，但在缺乏直接作用治疗的情况下，关于其基因型变异性和表型特性的数据有限。来

DESCRIPTION (provided by applicant): Co-infection with hepatitis C virus (HCV) has emerged as a major cause of morbidity and mortality for persons living with HIV/AIDS. Epidemiologic studies clearly indicate that HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes. However, non-structural regions of the HCV genome such as NS5B are subject to distinct selection pressures - purifying selection necessary to preserve enzymatic functions critical for viral replication, drug resistance mutations, and/or compensatory mutations - compared to structural genome regions. Despite the growing importance of NS5B as an emerging target of HCV therapy, limited data are available regarding its genotypic variability and phenotypic properties in the absence of directly acting therapies. To address this substantial gap in our understanding of HCV replication and pathogenesis, we propose a comprehensive analysis of NS5B genotypic, phenotypic, and biochemical variability in two well-characterized populations with HCV and/or HIV co-infection. Such studies are critical to facilitate the rational design and utilization of novel HCV therapies and significantly improve the clinical management and overall survival of persons with chronic HCV infection.