| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Although it is now accepted that there are correlations between human papillomavirus (HPV) types and specific cytopathic changes (HPV-type-specific cytopathic effect : CPE), the true mechanism of the CPE is still inknown. The cytopathic effects of HPV 1, the related HPV types (HPV 4, 60 and 65), HPV 88, HPV 95 are intracytoplasmic granular (Gr-), homogeneous (Hg-), filamentous (Fl-), fibrillar (Fb-) and Hg-like inclusions (ICBs), respectively.
In this study, two new types of HPVs, HPV 88 and HPV95, which are associated with fibrillar and Hg-like ICBs, respectively, are molecularly clomed. Our studies have also revealed the specific association of a protein coded for E4 gene of each HPV type with the different inclusion bodies.
Using a combined histological, immunohistochemical, DNA-DNA in situ hybridization and three-dimensional reconstruction analysis we first revealed that the human papillomavirus-associated plantar epidermoid cyst related to epidermoid metaplasia of the eccrine duct e
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pithelium.
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 ridge in such early wart lesion studied, suggesting that the epidermal stem cells located in the basal layer of the rete ridges are primary target cells of the HPV. When considered alongside the above mentioned data, our observation support the idea that HPVs uviversally target stem cells in the bottom of the deep rete ridges as well as in the bulge of the hair follicles. Less
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