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.
Neyts
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
De Clercq
E
E
D000180:Acrylic Resins / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D016264:Dextran Sulfate / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D006678:HIV / Q000187:drug effects; D006558:Herpes Genitalis / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D051379:Mice; D008812:Mice, Hairless; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology*; D013498:Suramin / Q000494:pharmacology
D000180:Acrylic Resins; D000998:Antiviral Agents; D016264:Dextran Sulfate; D000071228:Polyelectrolytes; D011108:Polymers; D013498:Suramin; C063252:sulfated acrylic acid-vinyl alcohol copolymer