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Infectious Diseases of Mice and Rats (1991)
Institute for Laboratory Animal Research (ILAR)

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96
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Disease due to MTV infection is age-dependent, i.e., experimental inoculation of the virus causes morphologic lesions and depression of immunologic functions only in mice infected as neonates (before 72 hours of age). The characteristic lesion is lymphoid necrosis in the thymus, lymph nodes, and spleen, with the thymus being most severely affected (Cross, 1973; Wood et al., 1981). Following intraperitoneal inoculation of virus into 24 hour-old mice, virus is first detectable in the thymus on day 3, reaches peak titer on day 7, and disappears by day 14. Macroscopic necrosis of the thymus begins on day 7 and is most severe between days 10 and 14. Intranuclear inclusions are present in thymocytes on days 5 through 10. The weight of the thymus is reduced to only 25% of normal. Subsequently, the necrosis is superseded by a diffuse "granulomatous" response with giant cells. The thymus regains normal histology around day 21 and normal weight by day 42. Necrosis and repair follow similar patterns in the lymph nodes and spleen. After neonatal infection, persistent infection of the salivary glands occurs, but the mice do not produce serum antibody (Cross et al., 1979). In contrast, adult mice infected with the virus develop persistent infections of the salivary glands and produce serum antibody, without the occurrence of lymphoid necrosis (Cross, 1973, 1979; Wood et al., 1981).

The severe lymphoid necrosis seen in mice neonatally infected with MTV involves mainly helper T lymphocytes (Cohen et al., 1975; Mosier et al., 1977) and cytotoxic T lymphocytes (Cohen et al., 1975). There is reduced responsiveness to the T cell mitogens concanavalin A and phytohemagglutinin (Cohen et al., 1975), and reduced graft-versus-host response (Cross et al., 1976). Immunosuppression peaks at about 4 weeks and appears to return to normal by about 12 weeks after infection (Cohen et al., 1975). B lymphocyte functions appear to be unimpaired (Cohen et al., 1975; Morse et al., 1976), except that neonatally infected mice do not produce antibody to the virus (Cross et al., 1979).

Diagnosis

Mice infected postnatally produce serum antibodies that can be detected by ELISA, IFA or CF tests, with the ELISA test being the most sensitive (Lussier et al., 1988 a,b). In cases where neonatal infection is suspected, evidence of MTV infection can be obtained by inoculating pathogen free neonatal mice with salivary gland homogenate, saliva, or other test material followed by histologic examination of their thymuses, lymph nodes, and spleens for lymphoid necrosis and intranuclear inclusions 10-14 days later (Cross, 1973; Wood et al., 1981). In vitro isolation of the virus is impossible as no cell culture system is known to support the growth of MTV (Osborn, 1982).

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