proportion of mouse sera that clearly reacted with MVM antigen in the IFA test yielded negative results in the HAI assay that was used for confirmation. Although some opined that the IFA test simply yielded false-positive reactions, others were suspicious that there was an agent (or agents) distinct from MVM circulating in laboratory mouse colonies. As we know, the latter was the case, and the discrepant results of the two tests were based on the fact that the IFA test permitted recognition of both structural and nonstructural proteins of parvoviruses. The nonstructural coding regions of MVM and the newly recognized mouse parvovirus (MPV) are essentially identical, whereas the structural regions (recognized by sera in the HAI assay) are quite divergent. It is likely that those differences in the structural region account for the fact that the humoral immune response protects only against homotypic parvovirus infections of mice (Hansen and others 1999).
The existence of a putative new parvovirus was supported by studies at Yale, where transmission within an enzootically infected breeding colony of mice was documented. Medium from cultured peripheral blood lymphocytes and explanted spleens of seropositive mice contained a substance that agglutinated mouse erythrocytes; however, the hemagglutination could not be inhibited by antibody to MVM, rat virus (RV), or H-1 virus (A.L. Smith, unpublished data). Several years later, a cellular immunology laboratory at the University of Chicago began to have difficulty maintaining cloned T cell lines. Some cell lines died suddenly, and others simply failed to thrive. The presence of aggregated mouse erythrocytes was perceived to be a reliable indicator of infection with a putative virus (McKisic and others 1993). Southern blot analysis revealed the presence of a parvovirus that was shown serologically to be distinct from both the prototype and immunosuppressive allotropic variants of MVM. Infected cultures responded poorly to specific antigen and to interleukin 2. The agent was presumably introduced into the laboratory by spleen cells used as feeders and/or substrates for producing growth factors in mixed lymphocyte cultures. That laboratory, as well as others concentrating on murine T cell immunology, had episodic difficulty maintaining T cell lines and clones. This may have been due to incomplete decontamination after infections were recognized—parvoviruses are notoriously stable in the environment. Retrospective serology confirmed that MPV has circulated in US mouse colonies at relatively high prevalence for more than 25 years (Jacoby and others 1996).
Mouse parvovirus has an ideal relationship with its natural host: Infected mice of all genotypes and ages so far tested remain clinically normal and manifest no pathologic changes. The virus does not follow all parvoviral dogma—for instance, adult mice are at least as susceptible as neonates to MPV infection (Smith and others 1993). This is in contrast to the situation with MVM and most other parvoviruses. The generally higher susceptibility of neonates is likely attributable to the requirement by parvoviruses of a cellular factor present during S phase for their own replication.