West Nile virus is a mosquito-borne virus that can cause severe neurological disease or death in susceptible individuals. In Science Translational Medicine, Lazear et al. report that IFN-λ lessens neurologic sequelae in infected mice by enhancing blood-brain–barrier function and restricting entry of the virus into the central nervous system (CNS). Mice that lack the IFN-λ receptor IFNLR1 harbor more virus in the CNS after infection with West Nile virus. IFN-λ does not elicit a cell-intrinsic effect in antiviral responses; instead, it acts on brain microvascular endothelial cells to enhance colocalization of the junction proteins claudin-5 and ZO-1 and thereby makes the blood-brain barrier less permeable to blood-borne viruses. Surprisingly, this response does not require signaling via STAT1 or protein synthesis. Nevertheless, these findings highlight a means for modulating CNS permeability by IFN-λ.

Sci. Transl. Med. 7, 284ra59 (2015)