Viral entry mechanisms: human papillomavirus and a long journey from extracellular matrix to the nucleus

Papillomaviruses are epitheliotropic non-enveloped double-stranded DNA viruses, whose replication is strictly dependent on the terminally differentiating tissue of the epidermis. They induce self-limiting benign tumors of skin and mucosa, which may progress to malignancy (e.g. cervical carcinoma). Prior to entry into basal cells, virions attach to heparan sulfate moieties of the basement membrane. This triggers conformational changes, which affect both capsid proteins, L1 and L2, and such changes are a prerequisite for interaction with the elusive uptake receptor. These processes are very slow, resulting in an uptake half-time of up to 14 h. This minireview summarizes recent advances in our understanding of cell surface events, internalization and the subsequent intracellular trafficking of papillomaviruses.