Study of rodent HCV-GBV like viruses

项目概要/摘要 丙型肝炎病毒（HCV）和人佩吉病毒（GB病毒C）在全球分布，感染2- 5%的人口。特别是缺乏针对这些病毒的易处理的动物模型， 对于HCV，已经阻碍了对感染、传播、毒力、免疫和 发病机制为了应对这一挑战，我们在小规模的 哺乳动物，包括野生啮齿动物。我们正在进行的研究结果首次确定， 几种新的肝炎病毒（HCV样病毒）和佩吉病毒（GBV样病毒）， 野生啮齿动物存在的基因，编码的蛋白质和翻译元件同源 这些在人类病毒中发现的病毒，使我们假设这些不同的啮齿动物病毒种类 与HCV或GBV-C的生物学特性相似。拟议的遗传和生物 这些新的啮齿动物病毒的特性将使开发温顺的动物 研究病毒-宿主相互作用的模型，并可能导致新的策略， 治疗干预我们提出了两个具体目标：目标-1：识别啮齿动物HCV和GBV-C 类病毒（HGLV），并描述其完整的基因组，自然宿主和物种 目的-2：研究HGLV感染，组织嗜性和发病机制， 自然宿主动物物种的实验感染。追求这些目标将导致 在组织中与人类同源物相似的新啮齿类HGLV种的鉴定 归经和发病机理。我们的研究结果将为HCV的研究开辟新的途径 和GBV-C样病毒，并将有助于确定病毒和宿主因素， 肝炎病毒和细小病毒组织和种属嗜性、持久性、毒力、免疫逃逸 和发病机制。

Project Summary/Abstract Hepatitis C virus (HCV) and human pegivirus (GB virus C) are globally distributed and infect 2- 5% of the human population. The lack of tractable animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity and pathogenesis. To address this challenge, we searched for their virus homologs in small mammals, including wild rodents. Results of our ongoing studies identify, for the first time, several new species of hepaciviruses (HCV-like viruses) and pegiviruses (GBV-like viruses) in wild rodents. The presence of genes, encoded proteins and translation elements homologous to those found in human viruses, lead us to hypothesize that these different rodent virus species resemble HCV or GBV-C in their biological properties. The proposed genetic and biological characterization of these novel rodent viruses will enable the development of tractable animal models with which to study virus-host interactions and may culminate in new strategies for therapeutic intervention. We propose two specific aims: Aim-1: Identify rodent HCV and GBV-C like viruses (HGLVs) and characterize their complete genomes, natural host and species tropism; and Aim-2: Investigate HGLV infection, tissue tropism and pathogenesis using experimental infections of natural host animal species. Pursuit of these aims will lead to identification of the new rodent HGLV species that are similar to their human homologs in tissue tropism and pathogenesis. Results of our studies will open up new avenues of research on HCV and GBV-C like viruses, and will help in identifying virus and host factors that determine hepacivirus and pegivirus tissue and species tropism, persistence, virulence, immune escape and pathogenesis.