A newly recognized parvovirus of laboratory rats, designated rat parvovirus type 1a (RPV-1a), was found to be antigenically distinct. It was cloned, sequenced, and compared with the University of Massachusetts strain of rat virus (RV-UMass) and other autonomous parvoviruses. RPV-1a VP1 identity with these viruses never exceeded 69%, thus explaining its antigenic divergence. In addition, RPV-1a had reduced amino acid identity in NS coding regions (82%), reflecting phylogenetic divergence from other rodent parvoviruses. RPV-1a infection in rats had a predilection for endothelium and lymphoid tissues as previously reported for RV. Infectious RPV-1a was isolated 3 weeks after inoculation of infant rats, suggesting that it, like RV, may result in persistent infection. In contrast to RV, RPV-1a was enterotropic, a characteristic previously associated with parvovirus infections of mice rather than rats. RPV-1a also differed from RV in that infection was nonpathogenic for infant rats under conditions where RV infection causes high morbidity and mortality. Thus, RPV-1a is the prototype virus of an antigenically, genetically, and biologically distinct rodent parvovirus serogroup.

Lymphocytotropic mouse parvoviruses can perturb immune responses. For example the recently identified mouse parvovirus designated MPV-1 persistently infects lymphoid tissues and interferes with the ability of cloned T cells to proliferate. As a consequence of these findings the present studies were undertaken to characterize further the immunomodulatory effects of MPV-1 on T cell-mediated immune responses in vivo and in vitro. To evaluate the effect of MPV-1 on CD8+ T cell-mediated responses sarcoma I (SaI) cells, devoid of class II major histocompatibility (MHC) antigens, were administered to MPV-1-infected adult BALB/c mice. MPV-1 infection accelerated tumor allograft rejection. Immunofluorescence staining and in situ hybridization studies of tumors suggested that direct infection of the tumor cells was not responsible for accelerated rejection. Furthermore, compared with uninfected mice, T cells from infected mice that had rejected SaI tumors had a diminished cytolytic capacity. Taken together these results suggest that MPV-1 may induce "bystander help." To examine the in vivo effect of MPV-1 on CD4+ T cell mediated responses adult mice were primed with ovalbumin (OVA) and infected with MPV-1. Spleen and popliteal lymph node cells from OVA-primed mice 3 or 7 days after MPV-1 inoculation had reduced proliferation responses, whereas the proliferative capacity of mesenteric lymph node cells from these mice was increased. Similarly, MPV-1 reduced cytokine-induced proliferation of allospecific CD8+ cloned L3 T cells and OVA-reactive CD4+ T cells without effecting cell viability. Since parvoviruses are widespread among laboratory rodents, these findings emphasize the importance of identifying and excluding parvovirus infections in mice used for transplantation studies and in cultures of mouse T lymphocytes.

Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from experimental infection of inbred Lewis rats with Seoul virus strain 80-39. Rats inoculated with virus intraperitoneally at 6 days of age became persistently infected without clinical signs. Tissues from Seoul virus-inoculated 6-day-old rats were assessed at 6, 9, and 12 weeks post-inoculation for viral RNA by RT-PCR and in situ hybridization (ISH) and for infectious virus by inoculation of Vero E6 cells. Virus was isolated from lung and kidney of infected rats at 6 weeks and viral RNA was detected in lung, kidney, pancreas, salivary gland, brain, spleen, liver and skin at 6, 9 and 12 weeks. Rats inoculated with Seoul virus intraperitoneally at 10 or 21 days of age became infected without clinical signs but had low to undetectable levels of viral RNA in tissues at 6 weeks post-inoculation. ISH identified vascular smooth muscle and endothelial cells as common sites of persistent infection. Cultured rat smooth muscle cells and to a lesser extent cultured endothelial cells also were susceptible to Seoul virus infection. Pancreatic infection resulted in insulitis with associated hyperglycemia. These studies demonstrate that infant Lewis rats are uniformly susceptible to asymptomatic persistent Seoul virus infection. Additionally, they offer opportunities for correlative in vivo and in vitro study of Seoul virus interactions in host cell types that support persistent infection.

These results suggest that MPV-1 infection of skin-grafted mice may disrupt normal mechanisms of peripheral tolerance and provide a unique model to study virus-induced autoimmunity.

The duration of infection with rat virus (RV), an autonomous rodent parvovirus, was examined at multiple intervals over 6 months in rats inoculated by the oronasal route at 2 days of age or 4 weeks of age and individually housed after weaning to prevent cross-infection. Infectious virus was recovered by explant culture from 32 of 80 rats inoculated as pups and was detected as late as 6 months after inoculation. Rats inoculated as juveniles developed acute infection, but virus was not detected beyond 7 weeks after inoculation. Tissues from rats in both age groups were surveyed for RV DNA by Southern blotting using a double-stranded DNA probe made from a 1700 bp cloned fragment of RV spanning map units 0.19-0.52. Band patterns representative of acute infection (juvenile rats) were consistent with the replicating form of RV DNA, whereas patterns representative of persistent infection (rats inoculated as pups) were suggestive of defective or non-productive viral replication.