MPV (Mouse parvovirus) Biology and Diseases of Mice
Robert O. Jacoby, James G. Fox, and Muriel Davisson
During the mid-1980s, serological testing revealed a murine parvovirus that was antigenically distinct from MVM (McKisic et.al., 1993). The virus was isolated following it’s decellular immunity. The virus grew lytically in a CD8+ T cell clone designated L3 and inhibited the proliferation of cloned T cells stimulated with antigen or interleukin 2 (IL-2). Additional isolates confirmed that these viruses are antigenically distinct from MVM. Thus, they constitute a second and distinct sero-group of murine parvoviruses. Molecular analysis of MPV indicates that regions encoding the NS proteins are similar to those of MVM, a finding that accounts for cross-reactivity between the viruses in generic serological tests. However, they differ significantly in regions encoding the capsid proteins, accounting for their antigenic specificity (Ball-Goodrich and Johnson, 1994). The prototype isolate was first called an “orphan” parvovirus of mice because its biology and significance were obscure, but it has subsequently been named mouse parvovirus (MPV). MPV is very difficult to grow in vitro. Immortalized T cells (L3) are the only cells found thus far to support replication of MPV.
MPV infection is clinically silent in infant mice and adult immunocompetent or immunodeficient mice.
Epizootiology. vSerologic evidence strongly suggests that MPV causes natural infection only in mice. Infection has circulated in mouse colonies in the United States for at least 30 years. Retrospective testing indicated that the prevalence of MPV approached 40% in the early 1970s, whereas only 7% of tested sera contained MVM antibody. In situ hybridization has identified the small intestine as a site of viral entry and early replication, but respiratory infection cannot be excluded. Based on these findings and initial transmission studies, MPV is thought to be transmitted primarily by fecal excretion and ingestion of contaminated material. There is no evidence of prenatal transmission. Initial studies indicated that munoral (e.g., passively or maternally acquired) immunity can protect against MPV infection. However, immunity to MVM may not confer cross-immunity to MPV (Hansen, et al., 1999). MPV causes persistent infection in infant and adult mice, a property that differentiates it from MVM. In situ hybridization studies detected viral DNA in the lymph nodes of experimentally infected adult mice for at least 9 weeks. Furthermore, infection has been transmitted by adults to naive casemates intermittently for u tot 6 weeks (Smith et al., 1993).
MPV appears to enter through the intestinal mucus, which is a site of early virus replication. Acute infection is widespread but mild, involving lung, kidney, liver, and lymphoid organs. Histological lesions are not discernible, despite the potential for cytolysis during parvovirus replication. Lymphocytotropism is a characteristic of acute and persistent MPV infection in infant and adult mice. During acute infection virus is dispersed within lymph nodes, but during persistent infection virus localizes in germinal centers.
Because infected mice do not manifest signs or lesions and the virus is very difficult to propagate in cell culture, detection and diagnosis rely on serology and molecular methods. A recently developed MPVF-specific ELISA that uses MPV VP-2 as antigen is a sensitive and specific assay that differentiates MPV from MVM (L. J. Ball-Goodrich, unpublished results, 2001). The MAP test also can be used to detect parvovirus infections but is relatively time-consuming and expensive. As noted for MVM, a generic PCR assay for murine parvoviruses, using conserved primer sequences that are conserved among murine parvoviruses, can be used as a screening test. PCR also can be used to detect MPV-specific sequences in the VP-2 gene. Although diagnostic PCR is sensitive and specific, it is effective only in actively infected animals and requires access to tissues that are usually obtained at necropsy. Therefore, its primary value is to confirm serological results.
MPV infection must be differentiated from MVM infection. Because both viruses are enterotropic and lymphocytotropic, serology and molecular hybridization must be used to distinguish between them.
Prevention and control.
The persistence of MPV in individual mice, its potential for provoking immune dysfunction, and the resistance of murine parvoviruses to environmental inactivation favor active control and prevention of MPV infection. Quarantine of infected rooms is appropriate. Elimination (depopulation) of infected mice should be considered if they are an immediate threat to experimental or breeding colonies and can b e replaced. For mice that are not easily replaced, virus persistence in the absence of transplacental transmission favors cesarean rederivation or embryo transfer as relatively rapid options to eliminate infection. Control of infection also should include environmental decontamination. Chemical disinfection of suspect animal rooms and heat sterilization of caging and other housing equipment are prudent steps. Prevention is based on sound serological monitoring of mice and surveillance of biologicals destined for inoculation of mice.
Murine parvoviruses can distort biological responses that depend on cell proliferation. For MPV, such effects are seen on immune function and include augmentation or suppression of humoral and cellular immune responses.