Type I IFN is the primary cytokine that is induced rapidly in response to viral infections. It amplifies immune responses through the IFN-signaling cascade24,25,46. However, its antiviral effect in the intestinal tract is less clear. In the present study, we investigated the ability of orally administered γ-PGA to induce an innate immune response and to mount an antiviral state in the ileum. Our results indicate induction of IFN-β production without elevating the level of proinflammatory cytokine by γ-PGA, a non-LPS TLR4 ligand, thereby predisposing the ileum to develop a robust antiviral innate immunity against norovirus.