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

人乳头瘤病毒型特异性细胞病变作用的分子病理学研究。

基本信息

批准号：
14570813
负责人：
EGAWA Kiyofumi
金额：
$ 2.18万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570813/
关键词：
Human papillomavirus HPV cytopathogenic effect Inclusion wart inclusion body HPV E4 stem cell eccrine gland ヒトパピローマウイルス足底表皮様嚢腫 CPE 細胞質内封入体 HPVE4 トノフィラメントケラチン

项目摘要

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.

虽然现在已经公认人乳头瘤病毒（HPV）类型与特异性细胞病变（HPV类型特异性细胞病变效应：CPE）之间存在相关性，但CPE的真正机制仍不清楚。HPV 1、相关HPV类型（HPV 4、60和65）和HPV 63的细胞病变效应分别是胞浆内颗粒状（Gr-）、均质（Hg-）和丝状（FI-）包涵体（ICB）。在这项研究中，Gr-ICBs的电子显微镜不同的形状，并包括聚集tonofibrient样的纤维状结构：汞-ICBs由聚集的颗粒状结构：和FI-ICBs的tonofibril样的厚纤维状结构和角质玻璃样颗粒状结构的混合物组成。我们的研究还揭示了每种HPV类型的E4基因编码的蛋白质与不同的包涵体的特异性联系。目前还没有证据表明手掌和脚底等无毛皮肤中存在HPV的靶细胞。一个问题是HPV是否靶向这些区域的表皮干细胞，Lavker和Sun已经证明这些区域位于猴子和人类手掌表皮的深网脊的基底层。为了验证这一假设，我们分析了疣的非常早期的病变，这些病变的大小足以估计疣和脊之间的相关性，并得出结论，疣最初只在掌跖皮肤的脊中发展。在显微镜下，使用从疣的整个身体获得的连续切片，在所研究的这种早期疣病变中，总是看到HPV相关的组织病理学变化仅限于深网脊，这表明位于深网脊基底层的表皮干细胞是HPV的主要靶细胞。我们的观察结果支持HPV普遍靶向深脊底部以及毛囊凸起处的干细胞的观点。