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

我们研究了HPV 1-，4-,60-，63-和65诱导的包涵疣，作为研究HPV型特异性细胞病变作用机制的模型系统。关于HPV 4/60/65相关的色素包络性疣，我们发现病变皮肤的黑色素细胞和角化细胞中黑色素颗粒的增加是疣色素沉着的主要原因，并且在疣中表达免疫组织化学HMB45，MART-1和酪氨酸酶相关蛋白的黑色素细胞数量增加，提示HPV型特异性激活黑色素细胞。电镜下，所有包涵体均与HPV型别特异性张力纤维/张力原纤维样结构相关，提示HPV型别可能影响角质形成细胞的型别特异性角蛋白代谢。我们还研究了HPV 1的生命周期，并将结果与其他类型的HPV进行了比较，发现HPV的生命周期在不同类型的HPV之间也存在差异。在包涵体疣中，我们发现了一种临床病理学上的新型包涵体疣，并刚刚开始从包涵体疣中克隆一种新型HPV。关于HPV相关的表皮样囊肿，我们不仅在囊肿中发现了一种新的HPV 57亚型，HPV 57c，而且通过三维重建分析，我们发现HPV 60相关的表皮样囊肿来源于内分泌管。

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.