Disc large 1 expression is altered by human papillomavirus E6/E7 proteins in organotypic cultures of human keratinocytes

M BUGNON VALDANO; F MARZIALI; E BOCCARDO; AL CAVATORTA; V DE SOUZA LINO; D GARDIOL; MG MORALE; RD STEENBERGEN

JOURNAL OF GENERAL VIROLOGY

SOC GENERAL MICROBIOLOGY

Lugar: London; Año: 2016

0022-1317

Loss of cell polarity is a fundamental process in cell transformation. Among polarity proteins,we focused on human disc large (DLG1), which is localized mainly at adherens junctions andcontributes to the control of cell proliferation. We previously demonstrated that its expression isaltered in HPV-associated cervical neoplastic lesions, but the mechanisms beyond this remainunknown. In this study, we analysed the contribution of HPV proteins to the changes in DLG1expression in the squamous epithelium. We observed tissue and intracellular misdistributionof DLG1 when high-risk HPV-18 E7 or E6/E7 proteins were expressed in organotypic raftcultures. The viral oncoproteins induce the loss of DLG1 from the cell borders and an increasein the level of DLG1 protein, reflecting the pattern observed in cervical lesions. These findingswere corroborated in cultures bearing the entire HPV-18 genome. Interestingly, changes intissue distribution and abundance of DLG1 were also detected in organotypic culturesexpressing the low-risk HPV-11 E7 or E6/E7 proteins, suggesting a conserved function amongdifferent HPV types. However, for low-risk HPVs, the subcellular localization of DLG1 atcell-to-cell contacts was predominantly maintained. This report offers new evidence, we believe,of the involvement of HPV proteins in DLG1 expression pattern and our data support previousobservations regarding DLG1 expression in cervical lesions.