Griffithsin protects mice from genital herpes infection. Medroxyprogesterone acetate-treated mice received a single dose of 0.1% GRFT or Carbopol gel intravaginally (20 μl). Fifteen minutes later, the mice were intravaginally inoculated with an LD50 (A) or LD90 (B) of HSV-2(4674) diluted in either PBS or pooled human seminal plasma (SP). Mice were scored for disease daily and were sacrificed if the score reached 4. Additional controls included mice that received no gel prior to challenge with virus in PBS. The number of mice in each group is indicated in the figure legend of the Kaplan-Meier survival curves; asterisks indicate P values of <0.05 (log rank test) (A and B). Disease scores for the 20 mice treated with Carbopol or GRFT gel and challenged with an LD50 of HSV-2 in PBS are shown in panel C, with average daily disease scores indicated above each bar. The asterisks denote that the difference in disease scores was significantly lower for GRFT- than for Carbopol-treated mice at each time point (P < 0.05; t test). Genital tract tissue was harvested 1 and 7 days postinfection, weighed, and homogenized, and supernatants were cultured on Vero cells to determine the amount of infectious HSV-2 present. Plaques were counted after 48 h; each dot represents an individual animal, and the line indicates mean ± SEM; day 1, P = 0.12; day 7, P = 0.07, unpaired t test.