Papillomaviruses (PV) replicate exclusively in the terminally differentiating epidermal cells of skin and mucosa in a strictly species-specific manner. They infect the basal cells of this tissue, to which they probably gain access via microlesions. Following delivery of virus DNA to the nucleus of infected cells, infection is established by the initial amplification of the viral genome as nuclear minichromosomes. The infection spreads by cell division during which the viral genome copy number per cell remains constant. The viral life cycle is completed by amplification of the viral genome in fully differentiated cells, structural (late) gene expression, and viral assembly. Progeny virions are shed within the dead squames of the terminally differentiating keratinocytes. Human PV (HPV) comprises a large group of viruses with more than 100 genotypes identified so far. They usually induce benign self limiting tumors of skin and mucosa, which rarely progress to carcinomas of the cervix, vagina, penis, anus and others. Progression usually requires persistent infection by high risk types, e.g. HPV16 and HPV18. Due to the high incidence of HPV in the general population, HPV infection is associated with more than 7% and 1% of cancers in women and men respectively.
The strict dependence of PV on terminally differentiating keratinocytes for completion of their replication cycle initially made the study of entry processes difficult. It was impossible to propagate virions in cell culture, and virus yields from natural lesions were low. In vitro data backed by in vivo studies suggest an elaborate sequence of cell surface events that includes retrograde flow along actin protrusions towards the cell body. In addition, it has become obvious that PV have evolved unique strategies for internalization and intracellular trafficking to overcome the challenges it faces by replicating in this terminally differentiating, stratified epithelium. This mini-review summarizes recent advances in our understanding of papillomavirus’ interactions with the host cell cytoskeletal elements.
The Cytoskeleton in Papillomavirus Infection. Viruses 2011, 3, 260-271
Cytoskeleton defines the shape and structural organization of the cell. Its elements participate in cell motility, intracellular transport and chromosome movement during mitosis. Papillomaviruses (PV) are strictly epitheliotropic and induce self-limiting benign tumors of skin and mucosa, which may progress to malignancy. Like many other viruses, PV use the host cytoskeletal components for several steps during their life cycle. Prior to internalization, PV particles are transported along filopodia to the cell body. Following internalization, retrograde transport along microtubules via the dynein motor protein complex is observed. In addition, viral minichromosomes depend on the host cell machinery for partitioning of viral genomes during mitosis, which may be affected by oncoproteins E6 and E7 of high-risk human PV types. This mini-review summarizes recent advances in our understanding of papillomavirus’ interactions with the host cell cytoskeletal elements.