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.

项目摘要/摘要 丙型肝炎病毒(丙型肝炎病毒)和人类巨细胞病毒(GB病毒C)分布全球，感染2- 占总人口的5%。尤其是缺乏针对这些病毒的易于处理的动物模型 对于丙型肝炎病毒，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，我们在小范围内搜索了它们的病毒同源基因 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(丙型肝炎病毒样病毒)和巨细胞病毒(GBV样病毒) 野生啮齿动物。同源基因、编码蛋白和翻译元件的存在 在人类病毒中发现的那些，让我们假设这些不同的啮齿动物病毒物种 在生物学特性上与丙型肝炎病毒或GBV-C相似。拟议的遗传和生物学 这些新型啮齿动物病毒的特征将有助于发展易驯服的动物 用于研究病毒-宿主相互作用的模型，并可能最终形成新的策略 治疗性干预。我们提出了两个具体目标：目标-1：识别啮齿动物丙型肝炎病毒和GBV-C 与病毒(HGLV)相似，并描述其完整的基因组、自然宿主和物种 和目标-2：研究HGLV感染、组织嗜性和致病机制 自然宿主动物物种的实验性感染。对这些目标的追求将导致 组织中与人类同源物相似的啮齿动物HGLV新种的鉴定 归性与病机。我们的研究成果将为丙型肝炎病毒的研究开辟新的途径 和GBV-C类病毒，并将有助于识别决定 肝病毒和巨细胞病毒的组织和物种趋向性、持久性、毒性、免疫逃逸 和发病机制。