Fig. 4

Antagonizing RANTES within CNS extends the survival of mice after TBEV infection. Mice were treated with Met-RANTES, vehicle, anti-RANTES mAb, or isotype-matched control Ab daily from day 2 to 8 after a primary TBEV infection. a Met-RANTES-treated mice exhibited a delay in mortality following lethal TBEV challenge. Mortality in each group was monitored daily for 14 days. Data were pooled from three independent experiments (total of approximately 18 mice per group). Statistical differences were evaluated using the Kaplan–Meier test for mortality. *P < 0.05, compared to vehicle-treated mice. b Anti-RANTES mAb-treated mice exhibited a delay in mortality following lethal TBEV challenge. Mortality in each group was monitored daily for 14 days. Data were pooled from three independent experiments (total of approximately 18 mice per group). *P < 0.05, compared to isotype Ab-treated mice. c, d Body weight changes of mice were monitored daily. For each time point, the measured values are the average of the surviving mice. Bars represent the means ± the standard deviations of three independent experiments (total of approximately 18 mice per group). e Infectious virus in brain tissues. No significant difference in virus titers was observed at day 2, 5, or 8 between Met-RANTES-treated mice and vehicle-injected mice or anti-RANTES mAb-treated and isotype Ab-injected mice. Bars represent the means ± the standard deviations of three independent experiments (n = 4 mice per group). NS not significant. f Met-RANTES or anti-RANTES mAb treatment reduced inflammatory cell accumulation (indicated by black arrows) in cerebral cortex sections, compared to results for vehicle- or isotype Ab-treated mice, respectively. The histopathological changes of PFA-fixed sections in cerebral cortex were examined by HE staining on day 8 p.i. The photomicrographs demonstrate representative images obtained from three independent experiments (n = 4 mice per group). Bars, 100 μm