INFECTIVITY AND PATHOGENESIS OF TISSUE CULTURE DERIVED HCV IN CHIMPANZEES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 HCV研究的最新进展导致了体外组织细胞培养方法的发展，用于HCV的复制。目前尚不清楚是否所有的体外衍生的HCV分离株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分离株是否具有感染性并在黑猩猩模型中引起发病。一次注射1 - 2只动物的特定HCV分离株，并使用血浆样本通过PCR分析监测感染证据。如果有感染的证据，则将获得额外的血液和肝脏活检样本， 病毒学和免疫学测定。如果没有感染的证据，则动物将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。HCV基因型1和2病毒库的谱系和良好表征的储备对于测试正在开发的用于治疗HCV感染的人的新药的抗病毒活性是必不可少的。此外，储备病毒制剂可用于确定正在开发的用于预防HCV感染的候选疫苗的效力。

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.