The effects of topical foscarnet in a new model of herpes simplex skin infection.
Because of the lack of agreement about the effects of topically applied antiviral agents on herpes simplex virus (HSV) skin infections in humans and in animals, an in-vivo human skin model of infection was developed. Human skin was grafted on to congenitally athymic nude mice and the therapeutic effects of topically applied viral DNA polymerase inhibitor phosphonoformate (foscarnet) on the course of the disease were studied. Following infection with HSV, the human skin grafts developed herpes vesicles similar to those seen in human skin in situ. Vesicles developed within three days of inoculation, and coalesced and crusted over by the fifth day post-inoculation. Healing of the wound did not occur and non-treated animals died approximately 13 days after inoculation. Treatment with topically applied foscarnet starting 24 h after inoculation suppressed both the development of the clinical signs of the disease and the replication of HSV in the grafted human skin. However, when therapy was withdrawn the symptoms of the disease proceeded to develop. Late onset (day two post-inoculation) of the foscarnet treatment was without effect on the course of the disease. Because foscarnet showed an antiviral effect when applied to infected human skin, the lack of effect of foscarnet in clinical studies on recurrent genital or labial herpes may be due to differences in the pathogenesis of the primary and recurrent infections.
D000279:Administration, Cutaneous; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D017245:Foscarnet; D006561:Herpes Simplex / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D010746:Phosphonoacetic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D016038:Skin Transplantation; D014183:Transplantation, Heterologous
D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D017245:Foscarnet; D010746:Phosphonoacetic Acid