Disc Large 1 expression is altered by Human Papillomavirus E6/E7 proteins in organotypic cultures of human keratinocytes.

BUGNON VALDANO M; CAVATORTA AL; MORALE MG; MARZIALI, F; DE SOUZA LINO, G; BOCCARDO, E; GARDIOL, D

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 mainly localized at adherens junctions and contributes to the control of cell proliferation. We previously demonstrated that its expression is altered in HPV-associated cervical neoplastic lesions, but the mechanisms beyond this remain unknown. In this study, we analyzed the contribution of HPV proteins to the changes in DLG1 expression in the squamous epithelium. We observed tissue and intracellular misdistribution of DLG1 when high-risk HPV-18 E7 or E6/E7 proteins were expressed in organotypic raft cultures. The viral oncoproteins induce the loss of DLG1 from the cell borders and an increase in the level of DLG1 protein, reflecting the pattern observed in cervical lesions. These findings were corroborated in cultures bearing the entire HPV-18 genome. Interestingly, changes in tissue distribution and abundance of DLG1 were also detected in organotypic cultures expressing the low-risk HPV-11 E7 or E6/E7 proteins; suggesting a conserved function among different HPV types. However, for low-risk HPVs, the subcellular localization of DLG1 at cell-to-cell contacts was predominantly maintained. This report offers new evidence that contributes to the understanding of the archetype of DLG1 expression observed in histological samples.