title: Hepatitis E Virus Circulation in Italy: Phylogenetic and Evolutionary Analysis.
abstract: BACKGROUND
  Hepatitis E virus (HEV), a major cause of acute viral hepatitis in developing countries, has been classified into four main genotypes and a number of subtypes. New genotypes have been recently identified in various mammals, including HEV genotype 3, which has a worldwide distribution. It is widespread among pigs in developed countries.
  
  
  OBJECTIVE
  This study investigated the genetic diversity of HEV among humans and swine in Italy. The date of origin and the demographic history of the HEV were also estimated.
  
  
  METHODS
  A total of 327 HEV sequences of swine and humans from Italy were downloaded from the national centre for biotechnology information. Three different data sets were constructed. The first and the second data set were used to confirm the genotype of the sequences analyzed. The third data set was used to estimate the mean evolutionary rate and to determine the time-scaled phylogeny and demographic history.
  
  
  RESULTS
  The Bayesian maximum clade credibility tree and the time of the most common recent ancestor estimates showed that the root of the tree dated back to the year 1907 (95% HPD: 1811 - 1975). Two main clades were found, divided into two subclades. Skyline plot analysis, performed separately for human and swine sequences, demonstrated the presence of a bottleneck only in the skyline plot from the swine sequences. Selective pressure analysis revealed only negatively selected sites.
  
  
  CONCLUSIONS
  This study provides support for the hypothesis that humans are probably infected after contact with swine sources. The findings emphasize the importance of checking the country of origin of swine and of improving sanitary control measures from the veterinary standpoint to prevent the spread of HEV infection in Italy.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Montesano
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Giovanetti
authors.affiliation: Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ciotti
authors.affiliation: Molecular Epidemiology and Microbial Evolution (FEMEM)/Epidemiology Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Institute Superiore di Sanita, Rome, Italy; Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cella
authors.affiliation: Molecular Epidemiology and Microbial Evolution (FEMEM)/Epidemiology Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Institute Superiore di Sanita, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lo Presti
authors.affiliation: ProxAgen Ltd, Sofia, Bulgaria.
authors.forename: Alba
authors.initials: A
authors.lastname: Grifoni
authors.affiliation: Laboratory of Infectious Diseases and Tropical Medicine, University of Milan, Milan, Italy.
authors.forename: Gianguglielmo
authors.initials: G
authors.lastname: Zehender
authors.affiliation: Clinical Pathology and Microbiology Laboratory, University Hospital Campus Bio-Medico, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Angeletti
authors.affiliation: Molecular Epidemiology and Microbial Evolution (FEMEM)/Epidemiology Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Institute Superiore di Sanita, Rome, Italy; Clinical Pathology and Microbiology Laboratory, University Hospital Campus Bio-Medico, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
keywords: Evolution; Hepatitis E Virus; Phylogeny