The molecular and pathological studies for human papillomavirus type-specific cytopathic effects

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We studied HPV 1-,4-,60-,63- and 65-induced inclusion warts as a model system for investigating the mechanism of HPV-type specific cytopathic effects. Concerning HPV 4/60/65-associated pigmented inclusion warts, we have revealed that increased melanin granules in both melanocytes and keratinocytes of the lesional skin are main contributors for the pigmentation of the warts and that the number of the melanocytes expressing immunohistochemically HMB45,MART-1 and tyrosinase-related proteins is increased in the warts, suggesting HPV type-specific activation of melanocytes. Electron-microscopically,all inclusion bodies were revealed to be associated with HPV type-specific tonofilamnt/tonofibril-like structures, suggesting that HPV types might influence type-specifically keratin metabolism of the keratinocytes.We also studied the life cycle of HPV 1 and compared the results with those of other types of HPV,revealing that the life cycle HPVs is also different between the distinct types or HPV. Among the inclusion warts,we have discovered a clinicopathologically new type of inclusion wart and have just started cloning of a new type of HPV from the inclusion wart.Concerning HPV-associated epidermoid cysts,not only that we demonstrated a new subtype of HPV 57,HPV 57c,in the cysts,but also that using three dimensional reconstruction analysis, we have revealed that a HPV 60-associated epidermoid cyst is derived from the eccrine duct.