BRIEF REPORT The emergence of genotypes 3 and 4 hepatitis E virus in swine and humans: a phylogenetic perspective Hongyan Xia • Niklas Wahlberg • Sa´ndor Bela´k • X. J. Meng • Lihong Liu Received: 8 July 2010 / Accepted: 21 September 2010 / Published online: 7 October 2010 Ó Springer-Verlag 2010 Abstract To investigate whether there is any phyloge- netic evidence to support the hypothesis that swine is the natural host of HEV genotypes 3 and 4, Bayesian analysis of 80 full-length genomic sequences of HEV was per- formed. The results showed that the strains of genotypes 3 and 4 from swine are paraphyletic with regard to strains of human origin, which are thus phylogenetically nested among the swine strains. Recognition of HEV genotypes 3 and 4 as viruses from swine or swine HEV can provide an evolutionary explanation to the observation of cross-spe- cies infection by genotypes 3 and 4 HEV. Keywords HEV  Evolution  Molecular epidemiology  Phylogeny Hepatitis E virus (HEV), the causative agent of acute hepatitis E in humans, is a single-stranded, positive-sense RNA virus. It belongs to the genus Hepevirus in the family Hepeviridae, which includes at least 4 recognized geno- types with 4 reference strains/isolates, Burma (genotype 1), Mexico (genotype 2), Meng (genotype 3) and T1 (genotype 4), according to the 8th report of the International Com- mittee on Taxonomy of Viruses [1]. Genotypes 1 and 2 HEV strains are mainly found in developing countries with poor sanitary conditions and are associated with large outbreaks and epidemics in humans in these regions. In contrast, genotypes 3 and 4 HEV strains infect both humans and other animal species, in particular, domestic pigs and wild boars, and are responsible for sporadic cases of acute hepatitis E in both developing and industrialized countries [2]. It has been recognized that hepatitis E is a zoonotic disease, and domestic pigs and wild boars are reservoirs for HEV. Since the first report on the identification of HEV in pigs [3], swine HEV has now been identified in essentially all swine-producing regions worldwide [4, 5]. According to a 2007 publication [6], more than 560 out of 1,439 HEV sequences in the GenBank database have originated from swine (HEV genotypes 3 and 4) in America, Europe, Asia, and Oceania. Up to 71% (2150/3009) prevalence of anti- HEV antibodies has been reported in Japanese pigs 3–6 months of age, and a high HEV viremia rate of 11% (190/1798) was found among pigs that are 2–4 month old [7, 8]. It has been demonstrated that viral sequences recovered from pig livers that were sold in local grocery stores are closely related, or identical in some cases, to the viruses recovered from human patients in Japan [9]. Most importantly, the contaminating virus in commercial pig livers sold in local grocery stores in the USA remains fully infectious [10]. Furthermore, sporadic cases of acute H. Xia  S. Bela´k Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 751 89 Uppsala, Sweden H. Xia  S. Bela´k  L. Liu (&) Joint R&D Division in Virology, The National Veterinary Institute, Swedish University of Agricultural Sciences, 751 89 Uppsala, Sweden e-mail: Lihong.Liu@sva.se N. Wahlberg Laboratory of Genetics, Department of Biology, University of Turku, 20014 Turku, Finland X. J. Meng College of Veterinary Medicine, Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA 123 Arch Virol (2011) 156:121–124 DOI 10.1007/s00705-010-0818-6