Furthermore, expression of Ifit2 mRNA in wt OB coincided with the presence of detectable levels of the encoded Ifit2 protein ( = P54) at 2 d.p.i. and 6 d.p.i., as seen by immunohistochemistry ( Figure 5C , and data not shown). Ifit2 protein staining was observed in VSV-infected cells within OB glomeruli as well as in surrounding and distant viral antigen-free cells, consistent with a remote IFN-dependent induction of Ifit2 expression ( Figure 5C , arrowheads in magnified images of right panel). Ifit1 and IFN-b mRNAs were induced as strongly in OB of Ifit22/2 as in wt mice, which correlated well with similar abundance of VSV RNA in wt and Ifit2 2/2 OB (Figure 5A compared to Figure 3C ). In brains, at 6 d.p.i., in contrast to OB, induction of Ifit1 and IFN-b mRNAs was considerably stronger in Ifit2 2/2 mice compared to wt mice ( Figure 5D , 5-fold and 27-fold, respectively, both p,0.005). The enhanced gene induction in VSV-infected Ifit2 2/2 mice was not restricted to specific regions of the brain ( Figure S2 ). Enhanced cellular gene expression also was observed for several virusinduced cytokine and chemokine genes, as measured by quantitative RT-PCR ( Figure S3A ). Gene expression profiling of brain tissue at day 6 d.p.i., using microarray analysis, revealed that many other genes, including ISGs, were also more strongly induced (Table S1 ). These results demonstrated that enhanced virus replication in the brains of Ifit2 2/2 mice led to enhanced type I IFN, other cytokines and ISG induction, which nevertheless failed to restrict VSV replication in the absence of Ifit2.