The levels of epithelial anchor proteins β-catenin and zona occludens-1 are altered by E7 of human papillomaviruses 5 and 8

J Gen Virol. 2016 Feb;97(2):463-472. doi: 10.1099/jgv.0.000363. Epub 2015 Dec 8.


Infection with viruses of the genus Betapapillomavirus, β-human papillomaviruses (β-HPV), is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and HPV8 in patients with the skin disease epidermodysplasia verruciformis (EV). The relocalization of the junctional bridging proteins β-catenin and zona occludens-1 (ZO-1) from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumour invasion. Here, we report that β-catenin and ZO-1 are strongly upregulated by the E7 oncoproteins of HPV5 and HPV8 in keratinocytes grown in organotypic skin cultures. Although the membrane-tethered form of β-catenin was elevated, no signs of β-catenin activity within the canonical Wnt signalling pathway could be detected. The upregulation of β-catenin and ZO-1 could also be confirmed in the skin of HPV8 transgenic mice as well as in cutaneous squamous cell carcinomas of EV patients. These data provide the first evidence that β-catenin and ZO-1 are direct targets of E7 of the oncogenic β-HPV types 5 and 8. The ability to deregulate these epithelial junction proteins may contribute to the oncogenic potential of these viruses in human skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betapapillomavirus / physiology*
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation
  • Host-Pathogen Interactions*
  • Humans
  • Keratinocytes / virology*
  • Mice, Transgenic
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Skin / pathology
  • Zonula Occludens-1 Protein / analysis*
  • beta Catenin / analysis*


  • Papillomavirus E7 Proteins
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • beta Catenin