Mouse Viruses
MVM (murine minute virus) Biology and Diseases of Mice
For many years, minute virus of mice (MVM) was recognized as the sole parvovirus of laboratory mice. Recent research has confirmed natural infections with a newly recognized serogroup. The prototype isolate was initially called mouse orphan parvovirus, but has been renamed mouse parvovirus (MPV).
Minute virus of mice (MVM) (murine minute virus) Etiology.
MVM is a small (5-kilobase) single stranded DNA virus. The prototypic strain is designated MVM(p). An allotropic variant with immunosuppressive properties in vitro also has been identified and is named MVM(i). The genome encodes two nonstructural proteins, NS-1 and NS-2, that are highly conserved among the rodent parvoviruses and account for prominent cross-reactivity in generic serological assays. The viral capsid proteins, VP-1 and VP-2, are virus-specific and form the basis for serological differentiation of MVM from mouse parvovirus (MPV). MVM has a broad in vitro host range. It replicates in monolayer cultures of mouse fibroblasts (A9 cells), C6 rat glial cells, SV40 (simian virus 40)-transformed human newborn kidney (342K cells), T cell lymphomas (EL4), and rat or mouse embryo cells, producing cytopathic effects that can include the development of intranuclear inclusions.
Clinical signs.
Natural infections are a symptomatic. Neonatal mice of some inbred strains are susceptible to lethal renal and/or intestinal hemorrhage during experimental MVM(i) infection, but this syndrome has not been reported in natural outbreaks.
Epizootiology.
MVM is perceived as a common virus of mice. Its prevalence in mouse colonies surveyed during the 1970s and 1980s was reported to be approximately 30-90%. A recent survey of major biomedical research centers revealed an overall prevalence of parvovirus infection of about 25% among specific pathogen-free mice and 40% among conventionally house mice (Jacoby and Lindsey, 1997). However, the earlier data did not account for MPV infections, which are now known to have been present during those decades, and the recent survey did not report results for MVM and MPV separately. Therefore, the true prevalence of MVM (as apposed to MPV) is unclear. The recent development of a strain-specific ELISA should resolve this issue.
MVM is highly infectious for the mouse, its only known natural host. Virus can infect the gastrointestinal track and is excreted in feces and urine. The resistance of rodent parvoviruses to environmental inactivation increases the risks of transmission after virus is excreted. Therefore, contamination of caging, bedding, food, and clothing must be considered a risk for spread of infection. Transmission occurs by oronasal exposure, but viral contamination of biologicals used for experimental inoculation, such as transplantable tumors, also can be a source of infection. Continuous contact exposure to infected animals or soiled bedding usually induces a humoral immune response within 3 weeks, but limited exposure may delay seroconversion. Young mice in enzootically infected colonies are protected by maternal antibody, but actively acquired immunity develops from infection sustained after the decay of maternal immunity. MVM, in contrast to MPV, is not thought to cause persistent infection; infection in immunocompetent adult mice usually lasts less than 3 weeks (Smith, 1983b; Smith and Paturzo, 1988). Infection appears to last less than 1 month even in oronasally inoculated neonatal mice. Although MVM has not been studied in immunodeficient mice, on should assume that infection will be prolonged in such mice. There is no evidence that MVM is transmitted in utero.
Pathology.
Natural infections or experimental inoculations of adult mice appears to be nonpathogenic, although low-level cytolysis in situ cannot be excluded. Contact-exposed neonates have been reported to develop cerebellar lesions, but these are very rare. Experimental infection of neonatal BALB/c, SWR, SJL, CBA, and C3H mice with MVM(i) can cause renal hemorrhage and infarction (Brownstein et al., 1991). DBA/2 mice also developed intestinal hemorrhages and accelerated involution of hepatic hematopoiesis. C57BL/6 neonates are resistant to vascular disease. This lesion has been attributed to viral infection of endothelium.
Diagnosis.
ELISA serology is the primary method to detect infection. Additionally, MVM can be differentiated from MPV using virus-specific VP-2 antigens (L.J. Ball-Goodrich, unpublished results, 2000). MVM infection also can be detected by PCR, in situ hybridization, and immunohistochemistry. Although the most commonly used molecular assay is PCR amplification of a conserved portion of NS-1, it does not differentiate MVM from MPV. However, virus-specific PCR assays that amplify gene segments within the capsid protein genes also are available (Besselsen, 1998). MVM can be isolated from spleen, kidney, intestine, and other tissues by inoculation of the C6 rat glial cell line. It also can be detected by the mouse antibody production test.
Prevention and control.
Because MVM does not persist in immunocompetent mice, control and elimination should exploit quarantine combined with thorough disinfection of the environment, because parvoviruses are resistant to environmental inactivation. However, there are no published reports confirming the success of the strategy. Additionally, reliance on quarantine presumes that MPV infection, which can be persistent in adult immunocompetent mice, has been ruled out. If the identification of the virus remains problematic, a more stringent approach such as cesarean rederivation or embryo transfer may be preferable. Prevention of MVM infection depends on strict barrier husbandry and regular surveillance of mice and mouse products destined for use in vivo.
Research complications.
MVM contamination of transplantable neoplasms is quite common; therefore, infection can be introduced to a colony through inoculation of contaminated cell lines. Failures to establish long-term cell cultures from infected mice or a low incidence of tumor "takes" should alert researchers to the possibility of MVM contamination. MVM(i) has the potential to inhibit the generation of cytotoxic T cells in mixed lymphocyte cultures.