Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, 34054, Republic of Korea.
Program of Immunology & Microbiology, Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
J Microbiol. 2021 Jun;59(6):616-625. doi: 10.1007/s12275-021-0690-y. Epub 2021 Mar 29.
Human papillomaviruses (HPVs) are known to utilize the down-regulation of epithelial (E)-cadherin, a major component of adherens junctions of keratinocytes, to evade host immune surveillance in high-risk group. However, the effects of HPV on the function of E-cadherin in low-risk groups remain unknown. We investigated whether type 2 HPV (HPV-2) E7 could induce alterations in E-cadherin expression in transiently transfected keratinocytes and cell lines expressing HPV-2 E7. To examine the expression pattern of E-cadherin in cutaneous warts and normal skin samples, immunohistochemical analysis was performed. Quantitative real-time polymerase chain reactions, luciferase assays, western blot, immunocytochemistry, and electron microscopy were used to evaluate the mRNA and protein expression levels of E-cadherin in normal human epidermal keratinocytes transfected with HPV-2 E7 plasmid DNA or E7-specific siRNA and in E7-expressing cell lines. E-cadherin expression levels in HPV-2 positive cutaneous warts were significantly decreased compared to those in normal skin (p < 0.05). Similarly, the mRNA and protein expression levels of E-cadherin in E7 transiently transfected cells were significantly decreased compared to those in empty vector-transfected cells. The decreases were restored by transfection with E7-specific siRNA (p < 0.05). Likewise, cell lines expressing E7 showed a decreased expression of E-cadherin. When the cells were cultured in low attachment plates, cell-to-cell aggregation was inhibited. Taken together, our data suggest that HPV-2 E7, the causative agent of cutaneous warts, could mediate the transcriptional repression of E-cadherin.
人乳头瘤病毒 (HPV) 被认为利用下调上皮 (E)-钙黏蛋白来逃避高危人群的宿主免疫监视，E-钙黏蛋白是角质形成细胞黏附连接的主要成分。然而，HPV 对低危人群中 E-钙黏蛋白功能的影响尚不清楚。我们研究了 2 型 HPV (HPV-2) E7 是否可以诱导瞬时转染的角质形成细胞和表达 HPV-2 E7 的细胞系中 E-钙黏蛋白表达的改变。为了研究 E-钙黏蛋白在皮肤疣和正常皮肤样本中的表达模式，进行了免疫组织化学分析。使用定量实时聚合酶链反应、荧光素酶测定、western blot、免疫细胞化学和电子显微镜来评估 HPV-2 E7 质粒 DNA 或 E7 特异性 siRNA 转染的正常人表皮角质形成细胞和 E7 表达细胞系中 E-钙黏蛋白的 mRNA 和蛋白表达水平。与正常皮肤相比，HPV-2 阳性皮肤疣中的 E-钙黏蛋白表达水平显著降低 (p < 0.05)。同样，瞬时转染细胞中 E-钙黏蛋白的 mRNA 和蛋白表达水平也明显低于空载体转染细胞。用 E7 特异性 siRNA 转染可恢复 E-钙黏蛋白的表达 (p < 0.05)。同样，表达 E7 的细胞系也表现出 E-钙黏蛋白表达降低。当细胞在低附着平板中培养时，细胞间聚集被抑制。综上所述，我们的数据表明，皮肤疣的致病因子 HPV-2 E7 可能介导 E-钙黏蛋白的转录抑制。
