Mechanisms of cell entry by human papillomaviruses: an overview

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.Human papillomaviruses (HPVs) are small, non-enveloped double-stranded DNA viruses that belong to the Papovaviridae family [1,2]. Scientific evidence accumulated from virological, molecular, clinical and epidemiological studies has identified HPV as the primary etiological agent in cervical cancer [1,3,4].Like other viruses, HPVs are obligatory intracellular parasites and must deliver their genome and accessory proteins into host cells and subsequently make use of the biosynthetic cellular machinery for viral replication [5,6]. The journey of a HPV particle from the cell surface to the cytosol and nucleus consists of a series of consecutive steps that move it closer to its site of replication. The viral capsid plays