The moleculo-pathologic study on Human papillomavirus type-specific cytopathogenic effect.

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Although it is now accepted that there are correlations between human papillomavirus (HPV) types and specificcytopathic changes (HPV type-specific cytopathic effect : CPE), the true mechanism of the CPE is still unknown. The cytopathic effects of HPV 1, the related HPV types (HPV 4, 60 and 65), and HPV 63 are intracytoplasmic granular (Gr-), homogeneous (Hg-) and filamentous (Fl-) inclusions (ICBs), respectively. In this study, Gr-ICBs electron-microscopically varied in shape and consisted of aggregated tonofilament-like fibrillar structures : Hg-ICBs consisted of aggregated granular structures : and FI-ICBs were composed of a mixture of tonofibril-like thick fibrillar structures and keratohyaline-like granular structures. Our studies have also revealed the specific association of a protein coded for E4 gene of each HPV type with the different inclusion bodies.There is as yet no evidence for the target cells of HPVs in hairless skin such as palms and soles. A question is whether HPVs target epidermal stem cells of such regions, which have been shown by Lavker and Sun to locate in the basal layer of the deep rete ridges of the monkey and human palm epidermis. To test the hypothesis, we analyzed very early lesions of the warts whose size was small enough to estimate the correlation between the warts and ridges, and have reached the conclusion that warts initially develop exclusively in the ridges of the palmoplantar skin. On microscopy, using serial sections obtained from the entire body of the warts, HPV-associated histopathological changes were always seen to be restricted to a deep rete ridge in such early wart lesions studied, suggesting that the epidermal stem cells located in the basal layer of the deep rete ridges are the primary target cells of the HPV.When considered alonside the above mentioned data, our observations support the idea that HPVs universally target stem cells in the bottom of the deep ridges as well as in the bulge of hair follicles.