Phylogeny and evolution of papillomaviruses based on the E1 and E2 proteins.

Papillomaviridae are a family of small double-stranded DNA viruses that infect stratified squamous epithelia in vertebrates. Members of this family are causative agents of malignant tumours, such as cervical cancer while others are associated with benign proliferative lesions. So far, Papillomaviruses (PVs) are classified according to the sequence identity in the capsid gene L1. However, evidence has accumulated indicating a discontinuity in the evolutionary history of the L1 and L2 genes of many PVs, giving rise to differences in the phylogenetic reconstructions of the early and of the late genes. Neither the oncogenes E5, E6 and E7 nor the upstream regulatory region are suitable for phylogenetic inference due to the poor conservation along the Papillomaviridae family. We have analysed here the evolutionary relationships of the PVs with respect to the E1 and E2 proteins, and the results provide both phylogeny and biologic behaviour of the viruses. The hierarchical taxonomic relationships can be structured as an alternative classification system in which mucosal high-risk viruses, mucosal low-risk viruses and viruses associated with cutaneous lesions are grouped separately and do not appear intermingled. Some important trends are also observed: first, evolution of the PVs has not been homogeneous, even in viruses that infect the same host, and second mucosal human PVs have evolved faster than their cutaneous counterparts. The evolutionary analysis based on the E1 and E2 proteins will allow us to better understand the generation of the diversity of the PVs and the development of malignancy associated with these viruses.