TREATMENT OF MURINE CYTOMEGALOVIRUS SALIVARY-GLAND INFECTION BY COMBINED THERAPY WITH GANCICLOVIR AND THYMIC HUMORAL FACTOR GAMMA-2

An optimal therapeutic regimen against primary CMV salivary-gland infe ction has not yet been developed. We used a murine CMV (MCMV) model sy stem to assess the ability of combined thymic humoral factor THF-gamma 2 immunotherapy and ganciclovir (GCV) antiviral chemotherapy to elimi nate detectable viral DNA from salivary glands of infected animals. Mi ce in different experimental groups were inoculated intraperitoneally with MCMV, treated, and then sacrificed either 2 weeks or 3 months lat er. To amplify and detect MCMV DNA in infected salivary-gland tissue, we developed a sensitive polymerase chain reaction (PCR) using a glyco protein B gene primer pair that amplifies a 356 bp segment. During the acute phase of the infection, the detection of high titers of infecti ous virus in the salivary glands correlated with a strong PCR amplific ation signal. Although active virions could not be recovered from untr eated animals 3 months after viral inoculation, the PCR assay detected a latent MCMV genome. Treatment with either GCV alone or THF-gamma 2 alone had little or no effect on the presence of MCMV DNA. By contrast , combined treatment with THF-gamma 2 and GCV significantly reduced th e amount of salivary-gland MCMV DNA to below the limit of PCR detectio n. The results presented here, and experimental data from previous MCM V research in our laboratories, imply that elimination of the virus fr om the salivary glands could be due in part to THF-gamma 2 restoration of the various MCMV-suppressed cell mediated immune-responses Combini ng THF-gamma 2 immunotherapy and GCV antiviral chemotherapy may-be an important step toward an effective therapeutic regimen that has the po tential to prevent the establishment of viral latency ensuing from pri mary MCMV salivary-gland infection.