Effect of polyanionic compounds on intracutaneous and intravaginal herpesvirus infection in mice: impact on the search for vaginal microbicides with anti-HIV activity.

Several polyanionic compounds were found to suppress intracutaneous infection of hairless mice with herpes simplex virus type 2 (HSV-2) only when present at the time of inoculation. Because (a) sexual intercourse is a major route of infection with human immunodeficiency virus (HIV); (b) due to the species-specificity of HIV, there is no small animal model to study intra-vaginal HIV infection; (c) HIV is equally or even more sensitive than HSV-2 to several polyanions; and (d) sulfated polymers may prevent the adhesion of (HIV-infected) lymphocytes to epithelial cells, we evaluated the effect of the compounds on intravaginal infection of mice with HSV-2. To this end, mice were infected intravaginally with a virus-compound mixture. Under the conditions used, the polysulfate dextran sulfate conferred only partial protection against infection and virus-induced mortality. However, PAVAS (a co-polymer of acrylic acid with vinylalcohol sulfate) completely protected against the infection. These results should be taken into account when planning clinical studies with a vaginal polysulfate formulation for the prevention of sexually transmitted HIV and/or HSV-2 infections.