FIG. 6.

Effects of tyrosine kinase inhibitors on VacV infection in mice. (a) Beginning 24 h prior to infection, 6-week-old C57BL/6 mice received PBS (carrier) or dasatinib (BMS-354825) continuously via a subcutaneous osmotic pump or twice daily by i.p. injection, at the concentrations indicated. Mice were infected i.n. with 2 × 10⁴ PFU VacV IHD-J (n = 6 mice per condition). (b) One day prior to infection, mice were implanted with subcutaneous osmotic pumps to deliver imatinib mesylate (STI-571; 200 mg/kg/day), dasatinib (BMS-354825; 0.5 mg/kg/day or 0.05 mg/kg/day), or both drugs in a single pump. Control mice received PBS (carrier). Four days after i.p. infection, viral genome copies were quantified by quantitative PCR. Each mouse is represented as a data point. Each horizontal line represents the median number of viral genome copies for each condition. (c) Effects of imatinib mesylate (STI-571; 200 mg/kg/day) delivered 24 h before, at the time of (0 h), or 24 or 48 h after i.n. infection with 2 × 10⁴ PFU VacV IHD-J. Carrier mice received PBS. Control mice were left uninfected. (d) Age-matched naïve controls, i.p. immunized mice, or mice treated with imatinib mesylate (STI-571; 200 mg/kg/day) that survived a previous challenge with the LD₁₀₀ (2 × 10⁴ PFU) of VacV IHD-J were injected i.p. with 10⁸ PFU of VarV IHD-J. The percent survival is plotted as a function of time after infection. (e) Six-week-old C57BL/6 mice were infected i.n. with 2 × 10² PFU IHD-J Luc, and luciferase activity was imaged at 2 days (2d) or 6 days (6d) postinfection. Animals received either PBS carrier or imatinib mesylate (STI-571; 200 mg/kg/day).