Dissemination and replication of MCMV after supraciliary inoculation in immunosuppressed BALB/c mice.

PURPOSE: To study replication and dissemination of murine cytomegalovirus (MCMV) in immunosuppressed (IS) and non-IS BALB/c mice after ocular inoculation via the supraciliary route.

METHODS

BALB/c mice were immunosuppressed by injections of methylprednisolone, and MCMV was injected via the supraciliary route. Ocular and nonocular tissues from both IS and non-IS mice were studied by plaque assay of tissue homogenates. The frequency of virus-positive leukocytes was determined by PCR.

RESULTS

In the inoculated eye, virus replication was significantly higher in both the anterior segment and the posterior segment of IS mice. Virus spread to extraocular sites in both IS and non-IS mice; however, significantly higher titers of virus were recovered from the salivary glands and lungs of IS mice than from non-IS mice, and clearance of virus from these sites was delayed in IS mice. Virus spread from the injected eye via leukocytes, and PCR amplification revealed that the frequency of virus-infected leukocytes was approximately 200-fold higher in IS mice.

CONCLUSIONS

The results of these studies suggest that immunosuppression significantly enhances virus replication in the inoculated eye, salivary glands, and lungs, leads to a higher frequency of virus-positive leukocytes, and delays clearance of virus from ocular and nonocular tissues. These results also suggest that retinitis in the injected eye of IS mice correlates with significantly higher titers of virus in the posterior segment.