Interferon-lambda in the Context of Viral Infections: Production, Response and Therapeutic Implications

Interferon (IFN)-lambda forms the type III IFN family. Although they signal through distinct receptors, type I (IFN-alpha/beta) and type III IFNs elicit remarkably similar responses in cells. However, in vivo, type III and type I IFN responses are not fully redundant as their respective contribution to the antiviral defense highly depends on virus species. IFN-lambda is much more potent than IFN-alpha/beta at controlling rotavirus infection. In contrast, clearance of several other viruses, such as influenza virus, mostly depends on IFN-alpha/beta The IFN-lambda receptor was reported to be preferentially expressed on epithelial cells. Cells responsible for IFN-lambda production are still poorly characterized but seem to overlap only partly IFN-alpha/beta-producing cells. Accumulating data suggest that epithelial cells are also important IFN-lambda producers. Thus, IFN-lambda may primarily act as a protection of mucosal entities, such as the lung, skin or digestive tract. Type I and type III IFN signal transduction pathways largely overlap, and cross talk between these IFN systems occurs. Finally, this review addresses the potential benefit of IFN-lambda use for therapeutic purposes and summarizes recent results of genome-wide association studies that identified polymorphisms in the region of the IFN-lambda 3 gene impacting on the outcome of treatments against hepatitis C virus infection. (C) 2014 S. Karger AG, Basel