INFECTIVITY AND PATHOGENESIS OF TISSUE CULTURE DERIVED HCV IN CHIMPANZEES

黑猩猩组织培养 HCV 的感染性和发病机制

• 批准号: 7957961
• 负责人: Krishna K Murthy
• 金额: $ 4.67万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-06 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957961
• 关键词: Animals; Biological Assay; Biopsy Specimen; Blood; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Dose; Funding; Genotype; Grant; Hepatitis C; Hepatitis C virus; Human; In Vitro; Infection; Institution; Methodology; Modeling; Monitor; Pan Genus; Pathogenesis; Pharmaceutical Preparations; Plasma; Preparation; Prevention; Primates; Research; Research Personnel; Resources; Sampling; Source; Testing; Time; United States National Institutes of Health; Virus; liver biopsy; tissue culture; vaccine candidate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent advances in HCV research has resulted in the development of in vitro tissuelcell culture methodologies for the replication of HCV. It is not clear whether all of the in vitro derived HCV isolates retain their infectivity and disease causing ability. The proposed studies will determine whether certain in vitro derived isolates of HCV are infectious and cause pathogenesis in the chimpanzee model. One to two animals at a time will be injected with a particular isolate of HCV and will be monitored for evidence of infection by PCR analysis using plasma samples. If there is evidence of infection then additional blood and liver biopsy samples will be obtained for virological and immunological assays. If there is no evidence of infection, then the animals will be injected with a higher dose of the same isolate or a different isolate and monitored for infection as described earlier. Pedigreed and well characterized stocks of HCV genotype 1 and 2 virus tocks are essential to test antivial activity of new drugs that are being developed for treating HCV infected humans. In addition, the stock virus preparations can be used to determine the efficacy of candidate vaccines that are being developed for prevention of HCV infection.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 HCV 研究的最新进展导致了用于复制 HCV 的体外组织细胞培养方法的发展。目前尚不清楚是否所有体外衍生的 HCV 分离株均保留其感染性和致病能力。拟议的研究将确定某些体外衍生的 HCV 分离株是否具有传染性并在黑猩猩模型中引起发病机制。每次将给一到两只动物注射一种特定的 HCV 分离株，并通过使用血浆样本进行 PCR 分析来监测感染证据。如果有感染证据，则将获取额外的血液和肝脏活检样本以进行治疗 病毒学和免疫学测定。如果没有感染证据，则将给动物注射更高剂量的相同分离株或不同分离株，并如前所述监测感染情况。纯种且特征明确的 HCV 基因型 1 和 2 病毒库存对于测试正在开发的用于治疗 HCV 感染人类的​​新药的抗病毒活性至关重要。此外，库存病毒制剂可用于确定正在开发的用于预防 HCV 感染的候选疫苗的功效。