Abstract
Parvoviruses have a predilection for rapidly dividing cells such as occurs during embryonic development. Potentially, in utero exposure could lead to immune tolerance in progeny mice. To determine if MPV infection in utero results in immune tolerance, pregnant mice were inoculated by oral gavage with 50 ID50 MPV1e or sham inoculated with phosphate buffered saline at day 5 and 12 gestation. Offspring were fostered to MPV-negative recipient dams prior to development of a milk spot. After confirming the offspring were seronegative for MPV by serology and not shedding by fecal PCR, they were challenged with 50 ID50 MPV1e by oral gavage at weaning or sham inoculated. At 4 weeks post inoculation, all weanlings exposed in utero developed antibodies to MPV, and MPV was detected by fecal PCR. Similarly, all weanlings from sham-inoculated dams challenged with MPV developed antibodies and MPV was detected by fecal PCR. None of the sham inoculated weanling mice from MPV infected dams or sham infected dams developed antibodies to MPV nor was MPV detected by fecal PCR. These results demonstrate that in utero exposure to MPV1e via oral gavage was insufficient to induce immune tolerance and provides greater confidence that rederivation techniques may successfully eliminate colonies of MPV. Furthermore, our findings do not provide evidence that MPV tolerance may contribute to hidden infections in mouse colonies.
Highlights
Mouse parvovirus (MPV) is a commonly recognized infectious agent relatively prevalent in mouse colonies and found in cell culture [1, 2] which can impact research results, such as potentiate rejection of tumor allograft [3]
Of the thirteen pregnant mice inoculated with MPV at day 5 and 12 gestation, eleven of them were confirmed infected by fecal PCR
Our hypothesis that mice exposed in utero develop tolerance to MPV infection resulting in the inability to mount a serologic response following post natal challenge with persistent infection was not supported in this study
Summary
Mouse parvovirus (MPV) is a commonly recognized infectious agent relatively prevalent in mouse colonies and found in cell culture [1, 2] which can impact research results, such as potentiate rejection of tumor allograft [3]. Elimination of MPV from infected colonies relies principally on rederivation; there are aspects of MPV infection that suggest mice may become immune tolerant, for example MPV has been detected in the gametes of mice [4,5]. There have been recent studies demonstrating rederivation by embryo transfer may not be effective at eliminating minute virus of mice (MVM), a parvovirus similar to MPV. In these studies, fertilized oocytes and morulae were exposed to varying concentrations of MVM. Recipient dams and their progeny receiving embryos infected with as little as 100 ID50 seroconverted to MVM. One plausible cause for this phenomenon is immune tolerance due to in utero exposure
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