Murine Norovirus Infection is Inhibited in Rag2 Gamma Chain- Deficient Mice after Oral Administration

A major step in murine norovirus (MNV) pathogenesis involves crossing the intestinal epithelial barrier to reach its target cells, macrophages, dendritic cells and B cells, for replication. Recent studies showed a decrease in MNV replication in the intestine after conditionally depleting mice of microfold (M) cells. To define the importance of Peyer’s patch M cells during MNV pathogenesis, mice deficient in recombination activation genes (Rag) and common gamma chain (γc) (Rag-γc^-/-) that do not develop Peyer’s patches and Peyer’s patch-associated M cells, were used. Rag-γc^-/- and immunocompetent Balb/c wild type (WT) controls were challenged intraperitoneally or per-orally with MNV-1 or CR3 for 24 and 72 hr. Both Rag-γc^-/- and WT mice showed similar intestinal titers following infection by the intraperitoneal route, which provides direct access to target cells. Although, Rag-γc^-/- mice have enhanced percentages of certain MNV target cells (i.e., dendritic cells and monocytes) in the small intestine, Rag-γc^-/- mice were not productively infected when virus was administered orally, a route when virions need to cross the intestinal epithelial barrier. These data demonstrate that MNV cannot cross the intestinal epithelium in the absence of Peyer’s patch M cells, indicating that they are the sole route for MNV-1 entry into the host interior in Balb/c mice.