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therapy was withdrawn the symptoms of the disease proceeded to develop.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.