Type I IFN blocks chimeric VSVs in human brain cultures. (A) Primary cultures of human brain astrocytes were pretreated with 0 (control), 1, or 10 U/ml of type I IFN for 18 h and then inoculated with the indicated chimeric VSVs (final concentration, 2 × 105 PFU/ml) or medium control and allowed to incubate for a further 24 h. The cells were then fixed and immunostained. The phase contrast images show typical cell density. The VSV-immunostained cultures show virus infection. Scale bar, 50 μm. (B) Percent infected cells in cultures without IFN pretreatment or with 1 U/ml IFN; 1 U/ml IFN was sufficient to completely block chimeric VSV infection, and 10 U/ml IFN (not shown) also completely blocked infection. The error bars indicate standard errors of the mean (SEM) (n = 3). (C) Three viruses, VSVΔG-H5N1, VSVΔG-CHIKV, and VLV, were injected intracranially into adult mice lacking type I IFN receptors. All three viruses were lethal within 1 week in all IFNR-KO mice tested.