Human Cytomegalovirus (HCMV) is a member of the Herpesviridae family which establishes life-long infections in their host after an acute infection. Global population studies have shown that the sero-prevalence of HCMV can range from 40-100% based on geo-location. HCMV generally spreads through bodily fluids, with cases showing active HCMV infections crossing the placental barrier. HCMV infections in immuno-competent hosts typically are asymptomatic but carry significant risk for fetuses and immunosuppressed patients. Infections can lead to fetal birth defects, or severe morbidity and mortality in the immunocompromised. Developing vaccines and treatments for life long HCMV infections have proven challenging and reinforces the need to understand HCMV’s life cycle and spread. Our lab has seen saliva has a prominent role in horizontal transmission, leading to new acute primary HCMV infections. HCMV replicates robustly in multiple organs, but replication in the salivary gland epithelium (hSGE) is tightly regulated, with hSGE infections proving particularly difficult for the immune system to clear. Such hSGE infections can take up to 6 months to clear the virus, in comparison to 14 days in other host organs. Our lab seeks to investigate the unique persistence that is found during hSGE HCMV infections. To achieve this, we have developed a primary salivary epithelial cell model and protocol for isolation, allowing us to generate primary salivary cell cultures in 3-D cultures or monolayers from patient samples. My project focuses on HCMV's ability to evade immune responses while present in the salivary gland, and the underlying cellular pathways it targets to achieve this. I approach this project using biochemical and molecular biology techniques, flow cytometry analysis, and epithelial/immune cell co-culture systems.