PATHOGENESIS OF MURINE PARVOVIRUS FIELD STRAINS

鼠细小病毒田毒株的发病机制

• 批准号: 6788817
• 负责人: DAVID G BESSELSEN
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-08 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6788817
• 关键词: Parvoviridae; age difference; animal colony; cell population study; cellular immunity; communicable disease transmission; epizootiology; gene expression; genetic screening; genetic strain; hematopoiesis; host organism interaction; humoral immunity; minute virus of mice; newborn animals; nucleic acid sequence; pathologic process; vertical transmission; virus cytopathogenic effect; virus diseases; virus genetics; virus infection mechanism

DESCRIPTION (provided by applicant): Minute virus of mice (MVM) and MPV are among the most prevalent infectious agents found in contemporary laboratory mouse colonies, and can potentially induce pathology, immunomodulation, or biomaterial contamination on the basis of experimentation with routine parvovirus laboratory strains. However, little is known about the strains of these viruses that are actually circulating in laboratory mouse colonies or the phenotypic effects associated with infection by these viral strains. Given the difficulties associated with murine parvovirus eradication, the high potential for their transmission among research facilities, and the rapidly expanding use of genetically altered mice, murine parvoviruses pose one of the most significant infectious disease problems in contemporary laboratory animal research. Several recently isolated or previously unrecognized strains of MVM and MPV have been obtained by our laboratory and shown to differ significantly from well characterized laboratory strains genetically, suggesting that in vivo infection by circulating field strains of MVM and MPV significantly differ from well characterized prototypic strains. The objectives of this proposal are to characterize the biology, epidemiology, pathogenesis, and host response to isolates of MVM and MPV that represent those circulating among contemporary laboratory mouse colonies. Three Specific Aims will be pursued: (1) Examine the prevalence of viral strains circulating within laboratory mouse colonies, isolate, and molecularly characterize strains that differ significantly from known strains, and characterize the in vitro host cell range for novel isolates and isolates already obtained; (2) Characterize the pathogenesis and transmission of murine parvovirus field strains to investigate the cellular and tissue tropism of viruses in various strains and ages of mice, the potential for persistent infection and reactivation of infectious virus production in persistently infected mice, and the potential for horizontal and vertical transmission; and (3) Characterize the host response to murine parvovirus field strains to investigate the humoral and cellular immune response, perturbations in hematopoiesis and host cell gene expression, the specific subpopulations of immune and hematopoietic cells infected by murine parvoviruses, and the roles of various immune system components on viral pathogenesis. These studies will provide critical information that can be applied to ensure accurate diagnosis, prevention of transmission, and eradication of these viruses from contemporary laboratory mouse colonies. In addition, these studies will provide information about perturbations in host physiology and gene expression induced by murine parvoviruses, and basic scientific information about parvovirus host interaction.

描述（由申请人提供）： 小鼠（MVM）和MPV的微小病毒是当代实验室小鼠菌落中发现的最普遍的传染剂之一，并且可能会根据常规的小腹病毒实验室菌株进行实验，潜在地诱导病理学，免疫调节或生物材料污染。 然而，对于这些病毒菌落中实际循环的这些病毒的菌株或与这些病毒菌株感染相关的表型作用，这些病毒的菌株知之甚少。 鉴于与消除鼠类细节病毒有关的困难，研究设施之间传播的高潜力以及迅速扩展的遗传改变的小鼠的使用，鼠细小病毒在当代实验室动物研究中构成了最重要的感染性疾病问题之一。 我们的实验室已经获得了几种最近分离或以前未被识别的MVM和MPV菌株，并证明在遗传上与表征良好的实验室菌株有显着差异，这表明MVM和MPV的循环场菌株在体内感染与良好特征性的原型株有显着差异。 该提案的目标是表征生物学，流行病学，发病机理以及对MVM和MPV分离株的反应，这些反应代表了当代实验室小鼠菌落中循环的生物学，发病机理和宿主反应。 将追求三个具体目标：（1）检查实验室小鼠菌落中循环，分离株和分子表征与已知菌株显着不同的菌株的病毒菌株的流行，并表征已经获得的新型分离株的体外宿主细胞范围； （2）表征小鼠各种菌株和年龄在各种菌株和年龄中病毒的细胞和组织疗法的发病机理和传播，持续感染和持续感染小鼠感染性病毒的潜力以及水平和垂直传播的潜力； （3）表征宿主对鼠细小病毒场菌株的反应，以研究造血和造血和宿主细胞基因表达的体液和细胞免疫反应，鼠类和造血细胞的特定亚群，由鼠聚调病毒感染的特定亚群以及各种免疫系统成分对病毒疗法的作用。这些研究将提供关键信息，可用于确保从当代实验室小鼠菌落中准确诊断，预防传播以及消除这些病毒。 此外，这些研究将提供有关鼠类细小病毒诱导的宿主生理和基因表达的扰动的信息，以及有关细节病毒宿主相互作用的基本科学信息。