3-HYDROXYPHTHALOYL BETA-LACTOGLOBULIN - IV - ANTIVIRAL ACTIVITY IN THE MOUSE MODEL OF GENITAL HERPESVIRUS-INFECTION

The spread of sexually transmitted infections caused by herpes simplex virus type 2 (HSV-2) has continued unabated despite educational effor ts generated in response to the human immunodeficiency virus (HIV) epi demic. Given the absence of effective vaccines, this indicates the nee d to develop prophylactic measures such as topical antiviral agents. C hemical modification of bovine beta-lactoglobulin (beta-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the genera tion of a potent HIV-1 inhibitor designated 3HP-beta-LG. This agent wa s shown to also have antiviral activity against HSV-2 and HSV-1 in vit ro. Recent studies indicate that 3HP-beta-LC binds to HSV-1 virions, w hich, at least in part, involves the viral glycoprotein gE. Here we sh ow that 3HP-beta-LC inhibits HSV-2 infection in the mouse model of gen ital HSV-2 infection. Simultaneous exposure to HSV-2 and 3HP-beta-LG c aused a significant decrease in the proportion of infected animals (27 % virus shedding, 5% lesion development and 0% fatality for 3HP-beta-L G as compared to 80% shedding, 60% lesion development and 53% fatality in mice treated with PBS). The proportion of animals with HSV-2 infec tion after treatment with beta-LG was similar to that in the PBS-treat ed group. Pretreatment with 3HP-beta-LG formulated in a gel, which pro longs the presence of the agent in the vagina, also significantly redu ced the proportion of HSV-2-infected mice (5% virus shedding, 5% lesio n development and 0% fatality for 3HP-beta-LG as compared to 70% shedd ing, 60% lesion development and 40% fatality in vehicle-treated mice). These differences were significant (P less than or equal to 0.0005, 0 .002 and 0.008 for shedding, lesion development and fatality, respecti vely). Virus titres in the minority of mice that developed infection w ere similar to those in untreated mice. HSV-2 infection was not inhibi ted by treatment of an ongoing infection, indicating that 3HP-beta-LC interferes with the initial infection. These data suggest that 3HP-bet a-LG may be an efficacious agent for preventing vaginal transmission o f genital herpesvirus infections.