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

虽然现在公认人类乳头瘤病毒(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的真实机制仍不清楚。HPV1及其相关类型(HPV4型、60型和65型)和HPV63型的细胞病变分别为胞浆内颗粒状(Gr-)、均质(Hg-)和丝状(F1-)包涵体(ICBS)。在本研究中，Gr-ICBS形态多样，由聚集的张力丝样纤维结构组成；HG-ICBS由聚集的颗粒状结构组成；FI-ICBS由张力原纤维样的厚纤维结构和角质透明样颗粒结构的混合物组成。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包涵体的特异性关联。目前还没有证据表明手掌和脚掌等无毛皮肤中存在HPV的靶细胞。一个问题是，HPV是否针对这些区域的表皮干细胞，Lavker和Sun已经证明这些细胞位于猴子和人类手掌表皮深网脊的基底层。为了验证这一假设，我们分析了疣的非常早期的病变，其大小足以估计疣和脊间的相关性，并得出结论：疣最初只在掌底皮肤的脊部发育。在显微镜下，使用从疣全身获得的连续切片，在所研究的这种早期疣病变中，HPV相关的组织病理学变化总是局限于深网脊，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。考虑到上述数据，我们的观察支持HPV普遍以深脊底部和毛囊隆起中的干细胞为靶细胞的观点。

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.