An optimal therapeutic regimen against primary CMV salivary-gland infection has not yet been developed. We used a murine CMV (MCMV) model system to assess the ability of combined thymic humoral factor THF-γ2 immunotherapy and ganciclovir (GCV) antiviral chemotherapy to eliminate detectable viral DNA from salivary glands of infected animals. Mice in different experimental groups were inoculated intraperitoneally with MCMV, treated, and then sacrificed either 2 weeks or 3 months later. To amplify and detect MCMV DNA in infected salivary-gland tissue, we developed a sensitive polymerase chain reaction (PCR) using a glycoprotein B gene primer pair that amplifies a 356 bp segment. During the acute phase of the infection, the detection of high titers of infectious virus in the salivary glands correlated with a strong PCR amplification signal. Although active virions could not be recovered from untreated animals 3 months after viral inoculation, the PCR assay detected a latent MCMV genome. Treatment with either GCV alone or THF-γ2 alone had little or no effect on the presence of MCMV DNA. By contrast, combined treatment with THF-γ2 and GCV significantly reduced the amount of salivary-gland MCMV DNA to below the limit of PCR detection. The results presented here, and experimental data from previous MCMV research in our laboratories, imply that elimination of the virus from the salivary glands could be due in part to THF-γ2 restoration of the various MCMV-suppressed, cell mediated immune-responses. Combining THF-γ2 immunotherapy and GCV antiviral chemotherapy may be an important step toward an effective therapeutic regimen that has the potential to prevent the establishment of viral latency ensuing from primary MCMV salivary-gland infection.
Bibliographical noteFunding Information:
We are grateful to Dr. Virginia Buchner for her helpful suggestions and for editing this manuscript. This work was supported in part by grants to BRZ from the Israel Association of Cancer, The Chief Scientist's Office Ministry of Health. SB is a recipient of a research fellowship from the Council of Research and Development, Ministry of Science. YB holds the Maynard Wishner Professorial Chair in Bio-Organic Chemistry and Malignant Diseases Research.
- Thymic humoral factor THF-γ2
- gB gene