FIG 1

DON treatment protects mice from NSV-induced acute disease. Six- to eight-week-old C57BL/6 mice were infected with 1,000 PFU of NSV intracerebrally and treated every 24 h intraperitoneally with the glutamine antagonist DON (0.3 mg/kg or 0.6 mg/kg), ACI (1 mg/kg), or PBS (100 to 200 μl) from the time of infection through day 7. (A) Clinical scores of treated and untreated mice (n = 6 for NSV, n = 12 for DON at 0.3 mg/kg, and n = 5 DON at 0.6 mg/kg). Clinical scores were as follows: 0 for no clinical signs, 1 for mild weakness, 2 for paralysis of one hind limb, 3 for paralysis of both hind limbs, and 4 for death. (B) Mortality of treated and untreated mice (n = 20 for NSV, n = 12 for DON at 0.3 mg/kg, and n = 15 for DON at 0.6 mg/kg). For PBS-treated mice (NSV), the median time of survival was 8 days, while DON-treated mice had median survival times of 14 days (0.3 mg/kg) and 12 days (0.6 mg/kg). ****, P < 0.0001 as determined by a log rank (Mantel-Cox) survival test. Data are pooled from results of 2 independent experiments. (C and D) Clinical scores (C) and mortality (D) of ACI-treated (n = 5) and PBS-treated (n = 5) mice. Gray shading designates the drug treatment period.