Abstract
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.
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Acknowledgements
We gratefully acknowledge Yang Hoon Huh for helping to perform the immune-EM analysis. This research was supported by a grant (2011-0010754) from the Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education, Republic of Korea. It was also supported by the 2013 Hannam University Research Fund.
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Ethics Statement All experimental procedures of this study were approved by the Institutional Review Board of Hannam University (IRB no. 14-02-02-0502).
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Song, J.Y., Park, Y.M. & Choi, S.Y. Type 2 human papillomavirus E7 attenuates E-cadherin expression in human keratinocytes. J Microbiol. 59, 616–625 (2021). https://doi.org/10.1007/s12275-021-0690-y
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DOI: https://doi.org/10.1007/s12275-021-0690-y