HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary Figures All Versions of this Article: vir.0.016295-0v1 91/2/521    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Barbaresi, S. Articles by Campo, M. S. Search for Related Content PubMed PubMed Citation Articles by Barbaresi, S. Articles by Campo, M. S. Agricola Articles by Barbaresi, S. Articles by Campo, M. S.

Effects of human papillomavirus type 16 E5 deletion mutants on epithelial morphology: functional characterization of each transmembrane domain

Silvia Barbaresi^1,,

Marc S. Cortese^1,

G. Hossein Ashrafi^1,

¹ Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK
² Section of Dermatology, Faculty of Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK
³ Division of Infection and Immunity, Faculty of Biochemical and Life Sciences, University of Glasgow, Glasgow G61 1QH, Scotland, UK

Correspondence
M. Saveria Campo
s.campo{at}vet.gla.ac.uk

Human papillomavirus type 16 (HPV-16) is the cause of cervical cancer. The HPV genome encodes three transforming proteins, E5, E6 and E7. E6 and E7 are the main transforming proteins of HPV, while the role of E5 is still poorly understood. Using three dimensional organotypic raft cultures we show that HaCaT human keratinocytes expressing HPV-16 E5 form a very perturbed epithelium, with simultaneous hyperkeratinization of some cells and defective differentiation of other cells. The basal layer is disturbed and many cells invade the collagen matrix. Many cells among the differentiated layers show characteristics of basal cells: progression through the cell cycle, expression of cytokeratin 14, lack of cytokeratin 1 and production of matrix metalloproteases (MMP). Using deletion mutants which encompass the three hydrophobic domains of E5, we have assigned the ability to promote invasion of the matrix to the first hydrophobic domain, and the capacity to induce MMP9 to the C-terminal four amino acids. We also show that invasion and production of MMP9 can be dissociated, as mutants that are still capable of invasion do not produce MMP9 and vice versa.

These authors contributed equally to this work.

Present address: ABBOTT srl, km 52, via Pontina, 04011 Aprilia, Italy.

Present address: School of Life Sciences, Kingston University London, Penrhyn Road, Kingston upon Thames KT1 2EE, UK.

Three supplementary figures are available with the online version of this paper.