FIG. 1.

Dose-dependent effects of IFN-α/β on replication of WN virus and induction of IFN-α/β in macrophages from flavivirus-susceptible and congenic resistant mice. (A) Macrophages from susceptible He and resistant RV mice were exposed to various amounts of mouse IFN-α/β of 1, 10, and 100 IU 24 h before being infected with WN virus at an MOI of 1. Average values for virus titers were derived from four experiments with 9 to 12 replicas per treatment and time point. Student's t test indicated a significant difference between control values and 10 and 100 IU of IFN-α/β for He samples at days 1 and 2 p.i. (0.01 < P < 0.05 and 0.001 < P < 0.01). IFN-α/β in a 10-IU dose had a significant effect on virus replication at days 1 to 3 (P < 0.001), and IFN-α/β in a 100-IU dose had a very significant effect for all time points in all samples from resistant RV mice (P ≪ 0.001). Standard error bars are included where appropriate. A dashed line denotes a threshold value of 2.0 log₁₀ TCID₅₀ units for accurate detection of virus titers, corresponding to 0.7 × 10² infectious particles per 100 μl. Virus was detectable below the 2.0 log₁₀ TCID₅₀ threshold as presented by two arbitrary values: one at 1.0 log₁₀ TCID₅₀ units, corresponding to viral titers between 0.70 × 10² and 0.35 × 10² infectious particles, and the other at 0.5 log₁₀ TCID₅₀ units, corresponding to viral titers between 0.35 × 10² and 0.10 × 10² infectious particles inclusive, all per 100 μl of cell supernatant. Virus was not detectable below 0.1 × 10² infectious particles/100 μl by this assay. (B) IFN-α/β production following WN virus infection in the presence or absence of prior treatment with IFN-α/β. The effect of 24 h of pretreatment with various doses of IFN-α/β on IFN-α/β production in WN virus-infected macrophages from susceptible He and resistant RV mice is shown. IFN-α/β levels were determined by the interferon bioassay in L929 cells. Supernatant collected from four experiments and eight replicas were combined and tested in four replicas by this assay and used for calculation of average values. Standard error bars are included where appropriate. A threshold dose of IFN-α/β that was determined by this assay was 2.5 IU/100 μl of supernatant.