INFECTIVITY AND PATHOGENESIS OF TISSUE CULTURE DERIVED HCV IN CHIMPANZEES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 丙型肝炎病毒研究的最新进展导致了用于复制丙型肝炎病毒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丙型肝炎病毒分离株都保留了它们的传染性和致病能力。拟议的研究将确定某些体外衍生的丙型肝炎病毒分离株是否具有传染性，并导致黑猩猩模型的发病。一次一到两只动物将被注射一种特定的丙型肝炎病毒分离物，并将通过使用血浆样本的PCR分析来监测感染的证据。如果有感染的证据，就会采集更多的血液和肝脏活检样本 病毒学和免疫学检测。如果没有感染的证据，那么动物将被注射更高剂量的相同的分离株或不同的分离株，并监测感染情况，如前所述。对于测试正在开发的用于治疗丙型肝炎病毒感染者的新药的抗菌活性，血统和特征良好的丙型肝炎病毒1型和2型毒株是必不可少的。此外，库存病毒制剂可用于确定正在开发的预防丙型肝炎病毒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.