PATHOGENESIS OF MURINE PARVOVIRUS FIELD STRAINS

点击翻译按钮获取中文摘要

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.