Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

Lee, Sanghyun; Baldridge, Megan T.

Interferon-lambda-mediated antiviral immunity in the intestine against rotavirus (EDIM-RV) and MNoV does not redundantly overlap with type I IFNs, while there is redundancy between type I and III IFNs to control influenza, SARS coronavirus, and respiratory syncytial virus in the lung, and herpes simplex virus-2 in the genital tract [reviewed in Ref. (76) ]. There are two potential reasons for a non-redundant role for IFN-λ in the intestine. First, the IFN-λ receptor is highly expressed in IECs but is minimally detectable in other intestinal cell types such as lamina propria cells (50) . Second, expression of IFN-α receptor subunits (i.e., IFNAR1 and IFNAR2) is less abundant in IECs than in lamina propria cells (14) , and surface expression of the IFN-α receptor is polarized to the apical side (41) . Interestingly, in neonatal mice, IECs are sensitive to both IFN-α/β and IFN-λ, and both IFN-α/β and IFN-λ can control RV (RRV strain) infection in suckling mice (24) . It has not been explored whether this IFN-α/β-sensitivity in neonatal IECs is from altered trafficking of the IFN-α receptor to the basolateral side. Further work is needed to explore the consequences of age-related IFN-α/β sensitivity in IECs and the pathogenesis of enteric virus infection (Figure 1) .