Epstein-Barr Virus (EBV) is a human herpesvirus that currently infects about 95% of the world’s population, and it establishes a lifelong infection with latency in long-lived memory B-cells. It is linked to various cancer types as well as autoimmune disorders, such as multiple sclerosis (MS). Inflammasomes are multiprotein complexes within the innate immune system and previous experiments suggest that certain inflammasome genes are elevated in MS. EBV receptor, CD21, has also shown to be internalized during active replication while inflammasome genes and inflammatory cytokines are upregulated. EBV primary infection and lytic activation is also correlated with increased CXCR3. CXCR3 and CXCR4 are chemokine receptors that have both been associated with enhanced neuroinvasion in mouse models. The first objective is to examine whether the inflammatory effects of EBV are mediated by its interaction with the CD21 receptor. The second objective is to use gene editing to interrogate the role of CD21, CXCR3, and CXCR4 in EBV-mediated inflammation and neuroinvasion. Data gathered from this project may help elucidate some of the mechanisms behind the immunopathology of MS, which is presently not well understood.