Proteomics of HCV Replication Complex

HCV 复制复合物的蛋白质组学

• 批准号: 7385667
• 负责人: Virendra Nath PANDEY
• 金额: $ 19.5万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-07 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385667
• 关键词: Affinity; Antibodies; Arts; Binding Proteins; Cells; Chronic Hepatitis C; Complex; Ectopic Expression; Genetic; Hepatitis; Hepatitis C; Hepatitis C virus; In Situ; In Vitro; Individual; Infectious hepatitides; Liver Cirrhosis; Liver diseases; Mass Spectrum Analysis; Mediating; Molecular; Nucleic Acids; Nylons; Pathogenesis; Peptides; Primary carcinoma of the liver cells; Production; Protein Binding; Proteomics; RNA; Role; Signal Transduction; Site; Small Interfering RNA; System; Technology; Viral; Viral Genome; Viral Proteins; Virion; Virus Diseases; Virus Replication; design; drug development; knock-down; prevent

DESCRIPTION (provided by applicant): Chronic infection by hepatitis C virus (HCV) is the leading cause of severe hepatitis, which often develops into liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms underlying HCV replication and pathogenesis are poorly understood. The identity of host or viral proteins relevant to the state of liver disease associated with HCV infection is not known. Although we have recently identified various cellular factors that interact with HCV 3'NTR (Appendix #1), nothing is known about the components of the HCV replication complex. These components are expected to have crucial roles in the production of infectious HCV virions. We have devised a means of capturing the replication complex in situ from HCV-infected cells and identifying its components by proteomics technology. We will investigate the implication of each identified cellular component on HCV replication by siRNA-mediated genetic knockdown of its expression in the cells. This will yield valuable information about the identity of the cellular or viral factors associated with the replication complex and facilitate the identity of new targets for use in preventing the viral infection.

描述（申请人提供）：丙型肝炎病毒（HCV）慢性感染是导致重症肝炎的主要原因，常发展为肝硬化和肝细胞癌。 HCV 复制和发病机制的分子机制尚不清楚。与 HCV 感染相关的肝病状态相关的宿主或病毒蛋白的身份尚不清楚。尽管我们最近发现了与 HCV 3'NTR 相互作用的多种细胞因子（附录#1），但对 HCV 复制复合体的组成成分仍一无所知。这些成分预计在传染性 HCV 病毒体的产生中发挥关键作用。我们设计了一种从 HCV 感染细胞中原位捕获复制复合物并通过蛋白质组学技术鉴定其成分的方法。我们将通过 siRNA 介导的细胞表达基因敲除来研究每种已识别的细胞成分对 HCV 复制的影响。这将产生有关与复制复合物相关的细胞或病毒因子的身份的有价值的信息，并有助于识别用于预防病毒感染的新靶标。