*Mice lacking Ifnlr1 in all cells or only in IECs exhibit higher viral shedding and intestinal titers of persistent murine NoV (MNoV)*Treatment with recombinant IFN-λ prevents and cures persistent MNoV infection, dependent on IEC expression of Ifnlr1*NoV dependence on the commensal microbiome for infection is absent in mice lacking Ifnlr1. Here, IFNLR1 is linked to infection.