Proteomics of HCV Replication Complex

HCV 复制复合物的蛋白质组学

• 批准号: 7828015
• 负责人: Virendra Nath PANDEY
• 金额: $ 23.4万
• 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 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7828015
• 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（由申请人提供）：丙型肝炎病毒（HCV）慢性感染是重型肝炎的主要原因，通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知之甚少。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。虽然我们最近已经鉴定出与HCV 3'NTR相互作用的各种细胞因子（附录#1），但对HCV复制复合物的组分一无所知。预期这些组分在感染性HCV病毒体的产生中具有关键作用。我们设计了一种方法，从HCV感染的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组分。我们将通过siRNA介导的基因敲低其在细胞中的表达来研究每个鉴定的细胞组分对HCV复制的影响。这将产生关于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，并促进用于预防病毒感染的新靶标的身份。

项目成果

Affinity capture and identification of host cell factors associated with hepatitis C virus (+) strand subgenomic RNA.

与丙型肝炎病毒 ( ) 链亚基因组 RNA 相关的宿主细胞因子的亲和捕获和鉴定。

• DOI: 10.1074/mcp.m112.017020
• 发表时间: 2013
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Upadhyay,Alok;Dixit,Updesh;Manvar,Dinesh;Chaturvedi,Nootan;Pandey,VirendraN
• 通讯作者: Pandey,VirendraN

Identification and evaluation of anti hepatitis C virus phytochemicals from Eclipta alba.

• DOI: 10.1016/j.jep.2012.09.036
• 发表时间: 2012-12-18
• 期刊: JOURNAL OF ETHNOPHARMACOLOGY
• 影响因子: 5.4
• 作者: Manvar, Dinesh;Mishra, Mahesh;Kumar, Suriender;Pandey, Virendra N.
• 通讯作者: Pandey, Virendra N.

Modulation of HCV replication and translation by ErbB3 binding protein1 isoforms.

• DOI: 10.1016/j.virol.2016.10.006
• 发表时间: 2017-01
• 期刊: Virology
• 影响因子: 3.7
• 作者: Mishra P;Dixit U;Pandey AK;Upadhyay A;Pandey VN
• 通讯作者: Pandey VN

Staufen1 promotes HCV replication by inhibiting protein kinase R and transporting viral RNA to the site of translation and replication in the cells.

• DOI: 10.1093/nar/gkw312
• 发表时间: 2016-06-20
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Dixit U;Pandey AK;Mishra P;Sengupta A;Pandey VN
• 通讯作者: Pandey VN

Affinity labeling of hepatitis C virus replicase with a nucleotide analogue: identification of binding site.

• DOI: 10.1021/bi301098g
• 发表时间: 2013-01-15
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Manvar D;Singh K;Pandey VN
• 通讯作者: Pandey VN