Fig. 8. IFN-λ enhances BBB tightness and restricts WNV neuroinvasion.

(A to C) Eight-week-old WT mice were treated with LPS, LPS and pegylated murine IFN-λ2 (25 mg via intravenous route), or PBS alone. BBB permeability was assessed 24 hours later by fluorescein or IgG permeation as described for Fig. 5. Symbols represent individual animals from two independent experiments. Values for LPS-treated mice were compared to mice receiving LPS + IFN-λ (t test). (A) Cortex: ****P < 0.0001, cerebellum: **P = 0.0096, spinal cord: **P = 0.0082. (C) Cortex: *P = 0.0348, cerebellum: *P = 0.0168. (D and E) Five-week-old WT mice were infected with 10² PFU of WNV via a subcutaneous route. On the day of infection and at days 2 and 4 afterward, 20 μg of pegylated murine IFN-λ2 protein (or PBS) was administered via an intravenous route. (D) Viral RNA in the plasma was measured on days 2 and 4 after infection. (E) Survival was monitored for 21 days after infection. n = 22 mice, *P = 0.0264 (log-rank test). (F and G) Nine-week-old WT mice were infected with 10² PFU of WNV via a subcutaneous route. At days 2, 3, and 4, 25 μg of pegylated murine IFN-λ2 protein (or PBS) was administered via an intravenous route. (F) Viral RNA in the plasma was measured on days 3,4, and5. (G) Viral burdeninthe CNS was measured by plaque assayatday 8. Symbols represent individual animals. Dotted lines represent the limit of sensitivity of the assay. ***P = 0.0009 (Mann-Whitney test).