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Open Access Highly Accessed Review

Mechanisms of cell entry by human papillomaviruses: an overview

Caroline AJ Horvath1, Gaëlle AV Boulet1, Virginie M Renoux3, Philippe O Delvenne3 and John-Paul J Bogers12*

Author Affiliations

1 Applied Molecular Biology Research (AMBIOR) group, Laboratory for Cell Biology and Histology, University of Antwerp, Antwerp, Belgium

2 Laboratory for Clinical Pathology (Labo Lokeren, campus RIATOL), Amerikalei 62-64, B-2000 Antwerp, Belgium

3 Department of Pathology, University of Liège, Liège, Belgium

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Virology Journal 2010, 7:11  doi:10.1186/1743-422X-7-11

Published: 20 January 2010

Abstract

As the primary etiological agents of cervical cancer, human papillomaviruses (HPVs) must deliver their genetic material into the nucleus of the target cell. The viral capsid has evolved to fulfil various roles that are critical to establish viral infection. The particle interacts with the cell surface via interaction of the major capsid protein, L1, with heparan sulfate proteoglycans. Moreover, accumulating evidence suggests the involvement of a secondary receptor and a possible role for the minor capsid protein, L2, in cell surface interactions.

The entry of HPV in vitro is initiated by binding to a cell surface receptor in contrast to the in vivo situation where the basement membrane has recently been identified as the primary site of virus binding. Binding of HPV triggers conformational changes, which affect both capsid proteins L1 and L2, and such changes are a prerequisite for interaction with the elusive uptake receptor. Most HPV types that have been examined, appear to enter the cell via a clathrin-dependent endocytic mechanism, although many data are inconclusive and inconsistent. Furthermore, the productive entry of HPV is a process that occurs slowly and asynchronously and it is characterised by an unusually extended residence on the cell surface.

Despite the significant advances and the emergence of a general picture of the infectious HPV entry pathway, many details remain to be clarified. The impressive technological progress in HPV virion analysis achieved over the past decade, in addition to the improvements in general methodologies for studying viral infections, provide reasons to be optimistic about further advancement of this field.

This mini review is intended to provide a concise overview of the literature in HPV virion/host cell interactions and the consequences for endocytosis.