(A and B) Organotypic brain slices from WT mice were cultured and infected with HSV-1 (1 × 10⁴ PFU) for 5 days in the presence or absence of caspase inhibitor Q-VD-Oph (100 μM). The viral titer and Ifnb mRNA levels in brain slices were measured and presented as mean ± SEM. (C and D) Mice were HSV-1 infected (4 × 10⁷ PFU/cornea) and treated on days 5, 6, and 9 after infection with Q-VD-Oph (20 mg/kg). Head swelling and weight change were monitored. The weight was normalized to day 5, when the treatment with Q-VD-Oph was initiated. (E) Viral titers (day 5 after infection) in the brainstems of mice infected with HSV-1 (2 × 10⁶ PFU/cornea) and then treated with vehicle or Q-VD-Oph (20 mg/kg) at days 3 and 4 after infection. (A–E) Data are presented as mean ± SEM and represent at least 3 independent experiments, n = 6–17 per group. P values were calculated by Wilcoxon rank-sum test (A, B, and E), 2-way repeated-measures ANOVA with Sidak’s multiple-comparison test (C and D). *0.01 < P < 0.05; **0.001 < P < 0.01; ****P < 0.0001. (F and G) WT mice were infected intracranially with HSV-1–expressing GFP (1 × 10⁷ PFU) and treated with the caspase inhibitor (zVAD) or vehicle as control (n = 4–6 mice/group) and figures represent 2 independent experiments. At 48 hours after infection, GFP-expressing brain biopsies (indicative for HSV-1 infection) were dissected. (F) Representative GFP expression in brain tissue and biopsies of HSV-1/GFP-infected mice. (G) Ifn-b and HSV-1 (gB) gene expression from the biopsies were quantified by real-time PCR. Values were normalized to β-actin and subsequently to similar biopsies from mock infected. Each row represents 1 biopsy and the biopsies are divided arbitrarily into 4 groups depending on the degree of infection defined by relative gB expression levels (2^–ΔΔCT): group 1: less than 3,000; group 2: 3,000–8,900; group 3: 8,900–29,000 and group 4: more than 29,000.