Herpes Simplex Virus 2 ICP0− Mutant Viruses Are Avirulent and Immunogenic: Implications for a Genital Herpes Vaccine
(A) HSV-2 shedding from the right eyes of mice inoculated with 100,000 pfu/eye of wild-type HSV-2 MS which were untreated or were treated with the antiviral drug acyclovir (ACV), as compared to mice inoculated in the right eye with (A) HSV-2 0Δ254 or HSV-2 0Δ810 or (B) HSV-2 0Δ104, HSV-2 0ΔNLS, or HSV-2 0ΔRING (n = 15 per group). ACV-treated mice were i. intraperitoneally administered 30 mg/kg ACV on Days −1, 0, 1, and 3 p.i., and were ii. orally administered 1 mg/ml ACV in their drinking water from Days −3 to +20 p.i. A double asterisk (**) denotes p<0.001 regarding the probability, p, that viral shedding on a given day was equivalent to HSV-2 MS-infected mice that received no ACV. (C) Representative sites of GFP-tagged ICP0 mutant protein expression in mouse corneas inoculated with HSV-2 ICP0− mutant viruses at 60 hours p.i. (D) Mean ± sd frequency of survival following inoculation with wild-type HSV-2 MS or HSV-2 ICP0− mutant viruses in two independent experiments, as determined on Day 30 p.i. (Σn = 25 mice per group). A double asterisk (**) denotes p<0.001 regarding the probability, p, that the frequency of survival was equivalent to HSV-2 MS-infected mice that received no ACV.