In France, Hepatitis E virus (HEV) is responsible of sporadic acute hepatitis cases whose origins and ways of transmission remain unclear. However, HEV is the only hepatitis virus to infect animal species other than human. The aim of this thesis was to evaluate the risk of zoonotic transmission from swine HEV to human. A first study of molecular epidemiology showed an active circulation of HEV between the human and swine populations, preferably foodborne. A second study by means of high-throughput sequencing showed the total adaptation of the HEV consensus genome and quasispecies during the inter-species transmission. A third study on three newly sequenced full-length HEV genomes from swine compared to available HEV genomes from humans did not reveal any major host restriction determinants within genotype 3. On the other hand, it revealed the need to reconsider HEV subtype classification in light of the new sequences available. Finally, a reverse genetics system was set up to study the phenotypes of the new human and porcine HEV strains in hepatocyte cell lines. In conclusion, these results showed the zoonotic risk of HEV transmission from swine eaten in France and its full genomic adaptation to its two host species. HEV is a peculiar zoonotic RNA virus whose genetic variability depends on his curious epidemiology, which includes the possibility of foodborne transmissions from a domestic animal reservoir. Finally, this work sets up the perspectives for further phenotypic studies.
