EBV infection and immune response dynamics in human tonsil organoids 4366

Abstract Description Epstein-Barr virus (EBV) is a global health concern due to its association with lymphoma and autoimmunity. Developing preventive therapeutics for EBV has been challenging, largely because of limitations in current models. Human tonsil organoids provide an ideal model to investigate immune responses to EBV, as tonsils are the primary site of infection. Using tonsil organoids and a GFP-expressing EBV, we evaluated B cell phenotype, function, clonal expansion, and the cellular immune response following EBV infection. Our preliminary data reveal that infected B cells acquire a germinal center-like phenotype. Single-cell sequencing indicates that infected B cells exhibit an activated, proliferative phenotype and dominantly express EBV latent genes. The potential clonal relationship of these infected B cells is under investigation. In organoids, the frequency of infected B cells correlates with activated CD4 and CD8 T cell frequencies. In the absence of CD4 T cells, infected B cells increased, suggesting that CD4 T cells are critical to viral control. We also observed differential frequencies of infected B cells in tonsil organoids derived from EBV seropositive and seronegative individuals, with Th1 CD4 T cells limiting infection upon EBV re-exposure. Together, these data demonstrate the utility of the tonsil organoids for addressing critical questions in human EBV infection biology and the associated adaptive immune response in primary and secondary infection. Funding Sources Supported by Wellcome Leap HOPE Program (to L.E.W.); IFI Fellowship GU12093 (to M.T.M.) Topic Categories Viral Immunology (VIR)