Parvoviruses are among the most common infections of laboratory rats, and can be major impediments to the use of rats in research. Infections in fetal or infant rats can cause illness or death whereas nonlethal infections, which are much more common, can distort biological functions such as immunologic responses. Furthermore, rat parvoviruses can persist in rats and in the environment, increasing risks of infection among experimental and breeding colonies. Although the pathogenic effects of rat parvoviruses are attributable to lysis of mitotically active cells, the pathogenesis and sequelae of persistent infection are poorly understood. This gap in knowledge confounds the assessment, control, and prevention of infection by these widespread and troublesome viruses. The proposed research will explore nonlethal infection caused by rat virus (RV), the prototypic rat parvovirus, in established models of persistent and prenatal infection, and will emphasize the pathogenesis of persistent infection. The first Aim proposes to determine the pathogenesis of infection initiated in utero. Important aspects of virus-host interaction will be examined in four experiments under each Aim using methods including synchronized cell cultures, explant cultures, in situ hybridization (ISH), Southern and Northern analysis, polymerase chain reaction (PCR), polymerase chain reaction in situ, immunohistochemistry (IHC), and selective in vivo depletion of T lymphocytes with monoclonal antibodies. The development of persistent infection and the role of immune defenses in persistent infection will be examined. The effects of acute and persistent maternal infection on intrauterine infection during pregnancy will be assessed. The current Aims will also lay groundwork for future evaluation of the effects of RV infection on biological responses involving cell proliferation. Because the properties of RV infection to be studied resemble those of infection with human parvovirus B19, the research may contribute to understanding of persistent and prenatal human parvovirus infection by using animal models.