PATHOGENESIS OF MURINE PARVOVIRUS FIELD STRAINS

描述（由申请人提供）： 小鼠细小病毒（MVM）和MPV是当代实验室小鼠群体中发现的最常见的感染因子，并且基于常规细小病毒实验室毒株的实验，可能诱导病理学、免疫调节或生物材料污染。 然而，人们对实际上在实验室小鼠群体中传播的这些病毒株或与这些病毒株感染相关的表型效应知之甚少。 鉴于与鼠细小病毒根除相关的困难、其在研究设施中传播的高潜力以及基因改变小鼠的迅速扩大使用，鼠细小病毒构成当代实验室动物研究中最重要的传染病问题之一。 我们的实验室已经获得了几种最近分离的或以前未识别的MVM和MPV菌株，并显示出与遗传上充分表征的实验室菌株显著不同，这表明MVM和MPV的循环野外菌株的体内感染与充分表征的原型菌株显著不同。 本提案的目的是表征MVM和MPV分离株的生物学、流行病学、发病机制和宿主反应，这些分离株代表了在当代实验室小鼠菌落中传播的分离株。 将追求三个具体目标：（1）检查实验室小鼠菌落中病毒株的流行情况，分离并分子表征与已知毒株显著不同的毒株，并表征新分离株和已获得分离株的体外宿主细胞范围;（二）描述小鼠细小病毒野毒株的致病性和传播特性，以研究病毒在不同毒株和不同年龄小鼠中的细胞和组织嗜性。小鼠，持续感染的可能性和在持续感染的小鼠中感染性病毒产生的再激活，以及水平和垂直传播的可能性;和（3）表征宿主对鼠细小病毒野毒株的应答，以研究体液和细胞免疫应答，造血和宿主细胞基因表达的扰动，小鼠细小病毒感染的免疫和造血细胞的特定亚群，以及各种免疫系统成分在病毒发病机制中的作用。这些研究将提供关键信息，可用于确保准确诊断、预防传播和从当代实验室小鼠群体中根除这些病毒。 此外，这些研究将提供有关干扰宿主生理和基因表达诱导的小鼠细小病毒，和细小病毒宿主相互作用的基本科学信息。

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.