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.
Highlights
Human papillomaviruses (HPVs) are small, non-enveloped double-stranded DNA viruses that belong to the Papovaviridae family [1,2]
Most studies investigating the uptake of HPV16 concluded the involvement of clathrin-dependent endocytosis [63,64,65,66]
The most likely scenario for HPV entry includes cell surface binding of virions mediated via Heparan sulfate proteoglycans (HSPG)
Summary
Human papillomaviruses (HPVs) are small, non-enveloped double-stranded DNA viruses that belong to the Papovaviridae family [1,2]. In vitro experiments showed that cell surface dynamics of HPV indicated a transport mechanism along actin rich cell protrusions to access the endocytic machinery and enhance infectious entry This transport was facilitated by binding to receptors that were likely to interact with actin filaments to mediate the transport towards the cell body by retrograde flow. Most studies investigating the uptake of HPV16 concluded the involvement of clathrin-dependent endocytosis [63,64,65,66] In contrast to these studies, Spoden et al observed clathrin- and caveolae-independent internalization of HPV16 PsVs. Entry occurred by a mechanism that was resistant to combined siRNA-mediated down regulation of caveolin-1 and clathrin heavy chain as well as being resistant to over-expression of dominant negative mutants of caveolin-1 and eps-15, which plays a role in clathrin coated vesicle formation [58]. Another study showed that virus particles use the same clathrin-dependent endocytic pathway to enter DC and LC [52]
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