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

我们研究了HPV 1-、4-、60-、63-和65型诱导的包涵体疣作为研究HPV型特异性细胞病变机制的模型系统。关于HPV 4/60/65相关的色素包涵体疣，我们已经发现，在皮损皮肤的黑素细胞和角质形成细胞中增加的黑色素颗粒是疣色素沉着的主要贡献者，并且在疣中表达化学上HMB 45、MART-1和酪氨酸酶相关蛋白的黑素细胞的数量增加，表明黑素细胞的HPV类型特异性活化。电镜下观察到所有包涵体均与HPV型特异性张力蛋白/张力原纤维样结构结合，提示HPV型可能影响角质形成细胞的型特异性角蛋白代谢，我们还研究了HPV 1的生命周期，并与其他类型HPV的结果进行了比较，揭示了HPV的生命周期在不同类型或HPV之间也是不同的。在包涵体疣中，我们发现了一种新的临床病理类型的包涵体疣，并刚刚开始从包涵体疣中克隆一种新的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亚型57，HPV 57 c，而且还使用三维重建分析，我们已经揭示了HPV 60相关的表皮样囊肿来源于小汗腺管。

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.