PATHOGENESIS OF MURINE PARVOVIRUS FIELD STRAINS

描述(由申请人提供)： 小鼠微小病毒(MVM)和MPV是在当代实验室小鼠群体中发现的最普遍的感染性因素之一，在常规细小病毒实验室毒株的实验基础上，可能会导致病理、免疫调节或生物材料污染。然而，关于这些病毒的毒株实际上在实验室小鼠群体中传播的情况，或者与这些病毒株感染相关的表型效应，人们知之甚少。鉴于与根除小鼠细小病毒相关的困难，它们在研究机构之间传播的高潜力，以及转基因小鼠的迅速扩大使用，小鼠细小病毒构成了当代实验动物研究中最重要的传染病问题之一。我们实验室已经获得了几个最近分离的或以前未被识别的MVM和MPV毒株，这些毒株在基因上与特征良好的实验室毒株有显著差异，这表明在体内感染的MVM和MPV野毒株与特征良好的原型毒株有显著差异。该建议的目的是描述代表当代实验室小鼠群体中流行的MVM和MPV分离株的生物学、流行病学、发病机制和宿主反应。将追求三个具体目标：(1)检测在实验室小鼠群体中传播的病毒株的流行率，分离和鉴定与已知毒株显著不同的毒株，并表征新分离株和已获得的分离株的体外宿主细胞范围；(2)表征小鼠细小病毒野毒株的致病机制和传播，以调查病毒在不同品系和年龄的小鼠中的细胞和组织嗜性，持续感染小鼠的持续感染和重新激活感染性病毒生产的可能性，以及水平和垂直传播的可能性；(3)研究宿主对小鼠细小病毒野毒株的体液和细胞免疫反应、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致病中的作用。这些研究将提供关键信息，可用于确保从当代实验室小鼠群体中准确诊断、防止传播和根除这些病毒。此外，这些研究还将提供关于小鼠细小病毒对宿主生理和基因表达的扰动的信息，以及关于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.