The long-term goal of the proposed research is to characterize in vivo and in vitro a newly recognized lymphocytotropic parvovirus of laboratory mice, mouse parvovirus (MPV). MPV is a significant threat to biomedical research using mice because it interferes with immune function. However, MPV persistently infects adult mice, so it may serve as a model for persistent human parvovirus infection.
The specific aims are (1) to continue molecular characterization of MPV, (2)to extend studies of MPV pathogenesis, (3) to characterize the immune response to MPV, (4) to extend studies of functional effects associated with MPV infection, and (5) to identify host factors that may influence expression of MPV infection. Methods to be used include bacterial expression vector systems, polymerase chain reaction, immunoblotting, Southern and Northern blotting, immunohistochemistry, in situ hybridization, virus quantification, flow cytometry, and assays to assess humoral and cell-mediated immunity. The capacity of antibody to neutralize MPV and to prevent infection and/or persistence when passively administered will be determined. The role of lymphoid cells in the host response will be evaluated in SCID and athymic mice and in immunocompetent mice depleted of CD4+ and/or CD8+ T cell subsets by serotherapy. If T cells play an important role, MPV-specific T cell clones will be generated for epitope mapping. Mice will be immunized with selected purified proteins to evaluate their capacity to protect upon live virus challenge. The functional effects of MPV infection will be assessed in vitro using proliferative and cytolysis assays and in vivo among mice that are sensitized to protein (ovalbumin) antigen, mice that bear skin allografts or mice that are tumor-challenged. Host facts that will be examined are age (neonate vs. weanling) and genotype, using genetically disparate inbred mouse strains.
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