Cho et al. characterized the distinct susceptibility of neuronal subtypes to infection with neurotropic viruses and associated this susceptibility with the differential expression of interferon (IFN)-stimulated genes (ISGs) and other IFN signalling components. Granule cells (which are neurons of the cerebellum) were more responsive to stimulation with IFNβ and less susceptible to infection with West Nile virus (WNV) than neurons of the cerebral cortex. Moreover, both basal expression and IFNβ-induced expression of IFN-related genes were higher in granule cells than in cortical neurons. Transfection of cortical neurons with granule cell-expressed ISGs identified a role for Ifi27, Irg1 and Rsad2 in protection against WNV infection. Interestingly, the differential expression of ISGs and other IFN signalling components in neuronal subtypes seem to involve the miRNA-132-dependent regulation of histone acetylation.