Grant: Project Grant

Based on our published and preliminary data using both mouse models and humanized mice, we have described the ability of latent gammaherpesviruses, including EBV to modulate the immune response towards pathogenic autoimmune disease. We propose to generate novel human HSC reconstituted humanized mice, infect these mice with EBV, and once latent infection is established, challenge these mice with different autoimmune diseases representative of human disease such as multiple sclerosis, rheumatoid arthritis and psoriatric arthritis. We aim to develop this model to explore the role of latent EBV infection in the initiation of disease when an autoimmune response is prompted by an intrinsic or extrinsic event. The resulting model will be used to determine consistencies or unique EBV-related immune responses affected by differential pathways of autoimmune initiation, and in using humanized mice, we will have the basis of a model to test whether removal of virus alters disease establishment and progression. We propose to administer three different interventions prior to and after latent infection with EBV and examine the effect on autoimmune disease induction. These interventions include Kick and Kill, and CAR-T cell approaches, all of which are used in other infection and cancer models and will be applied here to uniquely remove latent EBV virus.