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

基因型

基本信息

批准号：
9267990
负责人：
JASON T BLACKARD
金额：
$ 29.94万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-02 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9267990
关键词：
AIDS/HIV problem Address Amino Acid Substitution Antiviral Agents Biochemical Biochemistry Chronic Hepatitis C Clinical Clinical Management Collaborations Data Development Disease Progression Drug resistance Epitopes Evolution Fibrosis Funding Genetic Genome Genotype HIV HIV therapy HIV/HCV Hepatitis Hepatitis C Immune Evasion Immune Targeting Immune response Immune system In Vitro Individual Infection Injecting drug user Liver diseases Medicine Mono-S Morbidity - disease rate Mutation National Institute of Drug Abuse Natural History New Agents Patients Persons Phenotype Polymerase Population Positioning Attribute Prevalence Property Proteins RNA RNA-Directed RNA Polymerase Reporting Research Resistance Risk Saints Structural Genes Structure Treatment outcome Universities Variant Viral Viral Genome Viral Load result Virus Virus Diseases Virus Replication Woman Work antiretroviral therapy co-infection college design epidemiology study improved in vivo inhibitor/antagonist liver development mortality novel pressure public health relevance research study resistance mutation treatment response viral RNA viral fitness virology virus genetics virus pathogenesis

项目摘要

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.

描述（由申请人提供）：与丙型肝炎病毒（HCV）共同感染已成为患有艾滋病毒/艾滋病患者发病率和死亡率的主要原因。流行病学研究清楚地表明，HIV/HCV共感染与HCV复制，纤维化增加和肝病的发展有关。 HIV还增加了HCV结构基因的准多样性。但是，与结构基因组区域相比，HCV基因组的非结构区域（例如NS5B）受到不同选择压力的影响 - 与病毒复制，耐药性突变和/或补偿性突变至关重要的酶促功能所需的纯化选择。尽管NS5B作为HCV疗法的新兴靶标的越来越重要，但在没有直接作用疗法的情况下，有关其基因型可变性和表型特性的数据有限。到在我们对HCV复制和发病机理的理解时，我们提出了对NS5B基因型，表型和生化变异性的全面分析，以解决HCV和/或HIV共同感染的两个良好特征群体中。此类研究对于促进新型HCV疗法的合理设计和利用至关重要，并显着改善了慢性HCV感染患者的临床管理和整体存活。