Study of rodent HCV-GBV like viruses

啮齿动物HCV-GBV样病毒的研究

• 批准号: 8638384
• 负责人: Amit Kapoor
• 金额: $ 22.36万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638384
• 关键词: Acute; Address; Animal Model; Animal Viruses; Animals; Biological; Biological Assay; Biological Models; Biology; Chronic; Collection; Coronavirus; Data; Deer Mouse; Development; Disease; Elements; GB virus B; GB virus C; Generic Drugs; Genes; Genetic; Genetic Variation; Genome; Genomics; Genotype; Goals; Hantavirus; Hepatitis C; Hepatitis C virus; Hepatitis C-Like Viruses; Herpesviridae; High-Throughput Nucleotide Sequencing; Histologic; Homologous Gene; Human; Human Virus; Immune; Immune response; Immunity; Immunologics; Immunoprecipitation; Infection; Integration Host Factors; Laboratories; Lead; Luciferases; Mammals; Molecular; Mus; Norovirus; Organ; Pathogenesis; Peromyscus; Phylogenetic Analysis; Population; Poxviridae; Predisposition; Primates; Property; Proteins; Rabies virus; Research; Rodent; SIV; Serological; Serum; Severities; Suspension substance; Suspensions; System; Therapeutic Intervention; Time; Tissue Sample; Tissues; Translations; Tropism; Viral; Virulence; Virus; Virus Diseases; genome sequencing; influenzavirus; innovation; insight; novel; novel virus; prevent; public health relevance; structural genomics; tissue tropism; tool; transmission process; virus host interaction; virus identification; virus pathogenesis

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.

项目概要/摘要 丙型肝炎病毒（HCV）和人类pegivirus（GB病毒C）在全球分布并感染2- 占人口的5%。缺乏针对这些病毒的易处理的动物模型，特别是 HCV 的感染、传播、毒力、免疫和 发病。为了应对这一挑战，我们在小样本中搜索了它们的病毒同源物 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 Pegiviruses（GBV 样病毒） 野生啮齿动物。存在与以下同源的基因、编码蛋白质和翻译元件 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 其生物学特性类似于 HCV 或 GBV-C。拟议的遗传和生物学 这些新型啮齿动物病毒的表征将使驯服动物的开发成为可能 研究病毒与宿主相互作用的模型，并可能最终产生新的策略 治疗干预。我们提出两个具体目标： Aim-1：识别啮齿动物 HCV 和 GBV-C 像病毒 (HGLV) 一样，并表征其完整基因组、自然宿主和物种 向性;目标 2：利用 HGLV 感染、组织向性和发病机制进行研究 自然宿主动物物种的实验感染。追求这些目标将导致 鉴定新的啮齿动物 HGLV 物种，其组织与其人类同源物相似 向性和发病机制。我们的研究结果将为 HCV 研究开辟新途径 和 GBV-C 等病毒，将有助于识别决定病毒和宿主的因素 肝炎病毒和佩吉病毒组织和物种趋向性、持久性、毒力、免疫逃逸 及发病机制。