Figure 7. CD40 restricts rVSV/EBOV GP infection within the first 12 hours of infection and exacerbates pathogenesis.

A) Survival curves of female WT (n=6) and CD40^−/− (n=4) mice treated with 1 μg anti-IFNAR (MAR-1) antibody one day prior to challenge with a sublethal dose of rVSV/EBOV GP. Mice were monitored daily. B) Survival curve of female Ifnar^−/− (n=9) and Ifnar/CD40^−/− (n=13) mice that were challenged with a dose of rVSV/EBOV GP which was sublethal to Ifnar^−/− mice by i.p. injection. Mice were monitored daily (DPI=days post infection). C) Survival curve of female Ifnar^−/− (n=6) and Ifnar/CD40^−/−(n=6) mice infected with a dose of rVSV/EBOV GP that was sublethal to Ifnar^−/− mice by retro-orbital injection. Mice were monitored daily. D) Female Ifnar^−/− (n=8) and Ifnar/CD40^−/− (n=8) mice were infected i.p. with a dose of rVSV/EBOV GP that is sublethal to Ifnar^−/− mice. Serum was collected at 12-hour intervals and viremia was assessed by end point dilutions on Vero cells. E/F) Female Ifnar^−/− (n=12) and Ifnar/CD40^−/− (n=12) mice were infected i.p. with a dose of rVSV/EBOV GP that is sublethal to Ifnar^−/− mice. At 24 or 48 hours following infection, mice were anesthetized, perfused through the heart with PBS, and euthanized prior to organ harvest. RNA was isolated and qRT-PCR analysis of viral mRNA was performed (E). In parallel organs were homogenized and titers were assessed on Vero cells (n=4 organs/group) (F). All experiments were performed three times. For all experiments, * indicates p<0.05.