Differential phenotypes and localization of CD8 T cell responses to acute and chronic viral infection

Abstract

Abstract Norovirus represents the major viral source of gastroenteritis worldwide and the leading cause of foodborne illness in North America. Most infections are acute, symptomatic, and rapidly cleared but some cases persist asymptomatically or induce post-infectious irritable bowel syndrome. Despite the global economic burden of these infections no vaccine to prevent disease exists. Using immune correlates of acute vs chronic infection in mouse models following infection with related strains of murine norovirus, MNV-CW3 and MNV-CR6 respectively, this research interrogates the mechanisms underlying strain-specific differential antiviral CD8 T cell responses. The phenotype and quantity of MNV specific CD8 T cells are analyzed by flow cytometry. Since MNV-CW3 and -CR6 replication is higher in the small and large intestine, respectively, immunofluorescent microscopy is used to determine whether CD8 T cells are preferentially recruited to either tissue. Combining these complementary techniques provides novel insight into mechanisms governing intestinal antiviral T cell responses. Preliminary data shows activated MNV-specific CD8 T cells first accumulate in the MLN, suggesting this is the site of immune activation following oral infection with either virus. However, the magnitude and kinetics of T cell activation are reduced in CR6-infected mice compared to CW3-infected mice. This data suggests that these highly related viral strains induce activation of distinct populations of, or pathways in, APC populations with long-lasting effects on the outcome of infection. These results may have broad impacts on our understanding of how non-latent, chronic viral infections persist within a host.