Phylogeography and phylodynamics of European genotype 3 hepatitis E virus

Hepatitis E virus is classified into four genotypes that have different geographical and host distributions. The main cause of sporadic autochthonous type E acute hepatitis in developed countries is genotype 3, which has a worldwide distribution and widely infects pigs. The aim of this study was to make hypotheses concerning the origin and global dispersion routes of this genotype by reconstructing the spatial and temporal dynamics of 208 HEV genotype 3 ORF-2 sequences (retrieved from public databases) isolated in different geographical areas.The evolutionary rates, time of the most recent common ancestors (tMRCAs), epidemic growth and phylogeography of HEV-3 were co-estimated using a MCMC Bayesian method.The maximum clade credibility tree showed the existence of two distinct main clades: clade A, which consists of only European subtypes (HEV-3e and 3f), and clade B, which consists of European subtype 3c and all of the Asian subtypes (3a, 3b and 3d) sharing a common ancestor, which most probably existed in Asia in 1920s. All of the North American isolates belonged to Asian subtype 3a.On the basis of our time-scaled phylogeographical reconstruction, we hypothesise that after originating in the early 1800s in Europe, HEV reached Asia in the first decades of 1900, and then moved to America probably in the 1970s-1980s.Analysis of the skyline plot showed a sharp increase of the number of infections between the 1980s and 2005, thus suggesting the intervention of new and highly efficient routes of transmission possibly related to changes in the pig industry.