Biology, evolution, and medical importance of polyomaviruses: An update

The family Polyomaviridae encompasses non-enveloped viruses with a circular dsDNA genome that is typically approximately 5000 bp in length. Originally isolated from mammals, polyomavirus sequences have now been detected in invertebrates, fish, amphibians, reptiles and birds, although it remains to be determined whether all these animals are genuine hosts. The genomes of all polyomaviruses encode at least two regulatory proteins (large and small tumour antigen) and two structural proteins (capsid proteins VP1 and VP2) whose functions have been defined. The large and small tumour antigens have domains conserved among the polyomaviruses, which are responsible for specific interactions with cellular proteins and may result in alteration of the cell cycle. Additional open reading frames (ORFs) are present in the genomes of the different polyomavirus species. Some of these ORFs are transcribed and translated in viral proteins, but their functions remain poorly understood. Polyomaviruses have a restricted host specificity. This may indicate that co-divergence with their hosts, which has been demonstrated in a few cases, was an important factor during polyomavirus diversification. However, a strict co-divergence scenario fails to explain family-wide patterns of diversity, suggesting an important contribution of lineage duplication and, possibly to a lesser extent, recombination and cross-species transmission. Polyomaviruses are pathogens that can cause various malignant and non-malignant diseases in birds and mammals, including humans, but so far they have not been linked to disease in lower vertebrates. In immunosuppressed individuals, reactivation of polyomavirus BK or JC can cause serious disease of the urogenital tract and brain, respectively, while Merkel cell polyomavirus is most probably associated with the development of a highly aggressive neuroendocrine skin tumour in elderly or patients with pre-existing conditions. This review provides an update on the life cycle, prevalence, disease association, and evolution of the viruses belonging to this family.