Transformation of human vaginal xenografts by human papillomavirus type 11: Prevention of infection with a microbicide from the alkyl sulfate chemical family

Xenografts of human vaginal epithelium were established in two separate graft sites, the renal capsule and the subcutaneous space, by implantation into athymic mice. In the case of subcutaneous xenografts, the vaginal lumen was maintained. Xenografts were uninfected or infected with cell-free extracts of human papillomavirus type 11 (HPV-11). Control tissues also included normal human vaginal epithelium. After 70-90 days in vivo, xenografts were harvested and assessed for morphologic transformation and production of HPV-11 macromolecules and virions. A major focus in developing vaginal xenografts with an accessible lumen was their utilization in identifying and testing topical microbicides, especially microbicides with ability to inactivate human papillomaviruses (HPVs). An alkyl sulfate surfactant, sodium dodecyl sulfate (SDS), was recognized to inactivate efficiently HPVs as measured by absence of morphologic transformation and lack of detectable HPV mRNA and proteins in xenografts infected with SDS- treated virus. These experiments are the first to indicate that infected vaginal xenografts transplanted in the renal capsule or healed, human vaginal xenografts implanted subcutaneously in athymic mice serve as suitable targets for productive infection and neoplastic transformation by HPVs. These human tissue xenografts are suitable for testing both the safety and efficacy of vaginal microbicides.