Loss of secretions from the salivary gland (SG) is a disease feature of Sjogren's Syndrome (SS) as well as certain viral infections, including HCV and HIV. We have found that murine cytomegalovirus (MCMV) infection of autoimmune-prone NZM2328 mice serves as a model for virus-induced exocrinopathy, displaying many SS-like disease features. Interestingly, MCMV can induce severe SG dysfunction within 2-7 days after intraperitoneal infection. MCMV replication within the gland was not directly responsible for dysfunction since NZM2328 mice secreted normally 7-14 days after low dose infection, despite high virus within the gland. Since the low dose regimen limited viral burden elsewhere in the animal, such as the spleen, SG dysfunction seemed to correspond with systemic viral load. Surprisingly, lymphocytes were not required for MCMV-induced dysfunction at day 7, including NK, T and B cells. At day 2, morphological alterations were noted in acinar epithelium and flow cytometric analysis revealed rapid changes in glandular monocytic populations. Ongoing experiments are examining a potential causal link between systemic immune responses and/or infiltrating inflammatory monocytes with morphological and functional changes within the salivary gland. Supported by NIH R01AI50072 and a Sjogren's Syndrome Foundation Student Fellowship