Cytomegalovirus infection of Brown Norway rats was studied after intraperitoneal or subcutaneous inoculation of virus. No clinical illness was apparent during the 1st month postinfection (p.i.). Low titers of virus were detected in many organs at day 4 p.i. for the intraperitoneally inoculated animals and at day 11 p.i. for those inoculated subcutaneously. Thereafter, the virus disappeared from all tested organs except the salivary glands, where it appeared on day 11 p.i. and reached high levels by 4 weeks p.i. Histologically, no abnormalities were observed. The virus had an immunosuppressive effect during the 1st week p.i., as indicated by the immune response to sheep red blood cells.

An experimental rat model to study acute cytomegalovirus infections is described. Eight-week old male Brown Norway rats, immunosuppressed by total body irradiation, were infected with rat cytomegalovirus (RCMV). The effects of infection were determined by survival rates and the presence of virus or viral components in different organs was assayed by plaque test, immunoperoxidase staining, dot-blot DNA hybridization and in situ DNA hybridization. At days 10-post infection nearly 90% of the animals had died. Spleen, liver and bone marrow were heavily infected. Interstitial pneumonia was observed. Pathological findings strongly resembled the full scale of lesions in human CMV infections. Anti-RCMV hyperimmune serum was effective against mortality from RCMV infection and viral spread to lungs and liver was prevented. This model is appropriate for studies on the pathogenesis and antiviral therapy of CMV infections in the immunocompromised host.

In 8 of 10 wild rats trapped in The Netherlands, an infectious viruslike agent was isolated predominantly from the salivary glands and could be serially passed in laboratory rats. In rat embryo cells a typical cytomegalo-like cytopathic effect was produced. The morphologic and cultural characteristics of the isolated agent were comparable with those of the mouse cytomegalovirus (MCMV). The virus-nucleocapsid had a size of 92 nm and was not ether-resistant. The extracellular nucleocapsids were often enclosed by an outer layer of very variable shape and size. The formation of Fc receptors on cells infected with the rat virus could be demonstrated. The wild rats possessed neutralizing antibodies to the isolated agent. The rat agent grew only in rat embryo fibroblast cells while MCMV grew in rat and mouse embryo cells. The rat agent gave plaques in REF monolayers. Electron microscope studies showed the presence of nucleocapsids in the nucleus.

This report described the infection of two strains of laboratory rats with a ratvirus (RA-1) with cytomegalovirus-like characteristics. The virus was detected in the spleens and kidneys during the first week post infection. In the salivary glands maximal virus titer was reached at one month post infection; thereafter the titer declined. In Lewis rats virus could be detected in the salivary homogenate of most animals at more than 12 months post infection. In BN rats, in contrast, virus became undetectable in the salivary glands of most animals 5 months after inoculation. However, administration of cyclophosphamide or X-irradiation resulted in reactivation of the virus in virtually all animals. Co-cultivation of spleen cells from either latently or chronically infected animals resulted in recovery of virus. The animals developed antibodies and a T-cell mediated virus specific cytotoxicity.

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