Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

Lee, Sanghyun; Baldridge, Megan T.

Although reoviruses are also in the Reoviridae family, in contrast to RVs, they are not generally associated with serious human disease. Recently, however, they have been implicated in the pathogenesis of celiac disease, suggesting the possibility of a previously overlooked role as an environmental inflammatory trigger (45) . Importantly, reoviruses have been used as a tractable experimental system for studies of viral pathogenesis in newborn mice (46) . Reoviruses induce type I and III IFNs in a MAVS-dependent fashion (13, 15, 47) , likely via RIG-I-and MDA5-mediated sensing (48, 49) . Since these viruses exhibit a wide cellular tropism and a low degree of species specificity, reovirus infection of the mouse intestine is sensitive to both IFN-α/β and IFN-λ (14) . In adult mice, endogenous IFN-λ inhibits reovirus strain Type 3 Dearing replication in the intestine, and reovirus replicates exclusively in IECs of Ifnlr1-deficient mice (14) . By contrast, IFN-α/β inhibits reovirus replication in the intestine, but acts specifically on cells in the lamina propria. Another study using reovirus strain Type 1 Lang showed that endogenous IFN-λ inhibits reovirus replication in the mouse small intestine and that IFN-λ-receptor expression in IECs is critical for this antiviral activity (50) . Therefore, IFN-λ in the intestine controls reovirus replication in IECs, but IFN-α/β also coordinately controls reovirus infection in non-IEC cell types in the intestine.