Host IL-22 contributes to the establishment of chronic gammaherpesvirus infection 2650

Abstract Description Gammaherpesviruses are ubiquitous pathogens associated with various cancers including B-cell lymphomas. Gammaherpesviruses primarily target naïve B cells and drive a robust polyclonal germinal center response to increase their latent reservoir by manipulating B-cell differentiation to establish lifelong infection in memory B cells. The host factors exploited by gammaherpesviruses to establish chronic (latent) infection are largely unknown. IL-22, a member of the IL-10 family of cytokines, has a well-defined role in clearing bacterial and fungal infections. However, in viral infections, the role of IL-22 is unclear. Notably, there is no study that uncovers the role of IL-22 in gammaherpesvirus infection. Host IL-17A signaling has been reported to play a proviral role in chronic gammaherpesvirus infection. Given that IL-17A and IL-22 exhibit functional similarities in part while modulating germinal center reactions, it is worth exploring if IL-22, like IL-17A, has a role to play in gammaherpesvirus infection. Using murine gammaherpesvirus 68 (MHV68) as a tractable model, we report IL-22 as a contributory factor that promotes the gammaherpesvirus-driven germinal center response required for establishing chronic infection. We show that loss of IL-22 suppresses the gammaherpesvirus-driven germinal center response, establishment of viral latency, and viral reactivation. To our knowledge, this study is the first to unveil a proviral role of IL-22 in gammaherpesvirus infection. Funding Sources The work was supported by WMU Homer Stryker MD School of Medicine Startup grant. Topic Categories Viral Immunology (VIR)