The second aspect of murine norovirus infection that is of unknown relevance to human infection is the impressive capacity of MNV to infect lymph nodes draining the intestine (this paper and [31, 58, 59] ). This may be related to the tropism of MNV for dendritic cells and macrophages [28, 59] and likely reflects spread of MNV directly from the intestine, but may also reflect seeding of the MLN from systemic sites. Considering the distal ileum alone, B cells and MHC Class I and b2M were not required for live virus vaccination, and there was significant, but incomplete, protection in MHC Class II-/-mice ( Figure 3B and 3C). Consistent with this, studies of primary clearance showed that any single arm of the adaptive response was dispensable for ultimate control of primary infection in the intestine. However, vaccination-mediated control of infection in the MLN, and clearance of primary infection from the MLN [39] , required B cells. This differential requirement for components of the immune response in different organs raises an important question about norovirus pathogenesis and lymphoid infection: are the cells infected in intestine and MLN the same? Differences in viral tropism in the two tissues might explain the differential requirement for B cells between ileum and MLN, indicating the importance of future studies on the role of immunity in norovirus cell and organ tropism.