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Journal of Virology, August 2003, p. 8378-8385, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8378-8385.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Depletion of Langerhans Cells in Human Papillomavirus Type 16-Infected Skin Is Associated with E6-Mediated Down Regulation of E-Cadherin

Kate Matthews,1 Cheng Mee Leong,1 Lindsay Baxter,1 Emma Inglis,1 Kankatsu Yun,2 B. Thomas Bäckström,3 John Doorbar,4 and Merilyn Hibma1*

Virus Research Unit, Department of Microbiology,1 Department of Pathology,2 Malaghan Institute of Medical Research, Wellington School of Medicine, University of Otago, Dunedin, New Zealand,3 Virology Department, National Institute for Medical Research, London, United Kingdom4

Received 13 November 2002/ Accepted 7 May 2003

Human papillomavirus type 16 (HPV16) is an oncogenic virus that causes persistent infections in cervical epithelium. The chronic nature of HPV16 infections suggests that this virus actively evades the host immune response. Intraepithelial Langerhans cells (LC) are antigen-presenting cells that are critical in T-cell priming in response to viral infections of the skin. Here we show that HPV16 infection is directly associated with a reduction in the numbers of LC in infected epidermis. Adhesion between keratinocytes (KC) and LC, mediated by E-cadherin, is important in the retention of LC in the skin. Cell surface E-cadherin is reduced on HPV16-infected basal KC, and this is directly associated with the reduction in numbers of LC in infected epidermis. Expression of a single viral early protein, HPV16 E6, in KC reduces levels of cell surface E-cadherin thereby interfering with E-cadherin-mediated adhesion. Through this pathway, E6 expression in HPV16-infected KC may limit presentation of viral antigens by LC to the immune system, thus preventing the initiation of a cell-mediated immune response and promoting survival of the virus.

* Corresponding author. Mailing address: Virus Research Unit, Department of Microbiology, P.O. Box 56, Dunedin 9001, New Zealand. Phone: 643-479-7726. Fax: 643-479-7744. E-mail: merilyn.hibma{at}stonebow.otago.ac.nz.

Journal of Virology, August 2003, p. 8378-8385, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8378-8385.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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