Proteomic characterisation of secreted antiviral factors in cell-mediated immunity to human cytomegalovirus (360G-Wellcome-203747_Z_16_A)

Human cytomegalovirus (HCMV) is a widespread human pathogen, infecting 60-80% of the population. Infection is asymptomatic in immunocompetent individuals but causes disease in immunocompromised patients, such as transplant recipients. Current therapeutic tools are limited, with no available vaccine and a limited array of antivirals. HCMV triggers a broad and robust immune response involving both the innate and adaptive immune systems. Antiviral immunity is mediated in part by proteins secreted by immune cells and infected cells. In order to counteract this immunity, HCMV encodes numerous evasion factors that modulate the function of immune cells and the array of proteins they secrete (‘secretomes’). In this project, I will apply mass-spectrometry to generate comprehensive profiles of the secretomes produced by different immune cells when exposed to HCMV-infected cells. Using this technique, it will be possible to identify important and potentially novel secreted antiviral factors that can subsequently be validated and investigated to determine their mechanism of action. This will contribute to a better understanding of HCMV immunity and may facilitate the design of novel effective vaccine candidates and therapies.