title: Molecular evolution and antigenic variation of European brown hare syndrome virus (EBHSV).
abstract: European brown hare syndrome virus (EBHSV) is the aetiological agent of European brown hare syndrome (EBHS), a disease affecting Lepus europaeus and Lepus timidus first diagnosed in Sweden in 1980. To characterize EBHSV evolution we studied hare samples collected in Sweden between 1982 and 2008. Our molecular clock dating is compatible with EBHSV emergence in the 1970s. Phylogenetic analysis revealed two lineages: Group A persisted until 1989 when it apparently suffered extinction; Group B emerged in the mid-1980s and contains the most recent strains. Antigenic differences exist between groups, with loss of reactivity of some MAbs over time, which are associated with amino acid substitutions in recognized epitopes. A role for immune selection is also supported by the presence of positively selected codons in exposed regions of the capsid. Hence, EBHSV evolution is characterized by replacement of Group A by Group B viruses, suggesting that the latter possess a selective advantage.
authors.affiliation: CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos-Universidade do Porto/InBIO, Laboratório Associado, Vairão, Portugal; Departamento de Biologia, Faculdade de Ciências da Universidade do Porto, Porto, Portugal; INSERM, UMR892, CNRS, UMR6299, Université de Nantes, Nantes, France. Electronic address: analopes@cibio.up.pt.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Lopes
authors.affiliation: Istituto Zooprofilattico Sperimentale della Lombardia e dell׳Emilia Romagna, Via Bianchi 9, 25124 Brescia, Italy. Electronic address: lorenzo.capucci@izsler.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capucci
authors.affiliation: Department of Pathology and Wildlife Disease, National Veterinary Institute (SVA), Uppsala, Sweden; Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden. Electronic address: dolores.gavier-widen@sva.se.
authors.forename: Dolores
authors.initials: D
authors.lastname: Gavier-Widén
authors.affiliation: Anses, Ploufragan-Plouzané Laboratory, Avian and Rabbit Virology, Immunology, and Parasitology Unit, Ploufragan, France; European University of Brittany, Rennes, France. Electronic address: ghislaine.legall-recule@anses.fr.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Le Gall-Reculé
authors.affiliation: Istituto Zooprofilattico Sperimentale della Lombardia e dell׳Emilia Romagna, Via Bianchi 9, 25124 Brescia, Italy. Electronic address: emiliana.brocchi@izsler.it.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Brocchi
authors.affiliation: Istituto Zooprofilattico Sperimentale della Lombardia e dell׳Emilia Romagna, Via Bianchi 9, 25124 Brescia, Italy. Electronic address: ilaria.barbieri@izsler.it.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barbieri
authors.affiliation: INSERM, UMR892, CNRS, UMR6299, Université de Nantes, Nantes, France. Electronic address: agnes.quemener@nantes.inserm.fr.
authors.forename: Agnès
authors.initials: A
authors.lastname: Quéméner
authors.affiliation: INSERM, UMR892, CNRS, UMR6299, Université de Nantes, Nantes, France. Electronic address: jacques.le-pendu@univ-nantes.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Pendu
authors.affiliation: Sydney Emerging Infectious and Biosecurity Institute, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: jemma.geoghegan@sydney.edu.au.
authors.forename: Jemma L
authors.initials: JL
authors.lastname: Geoghegan
authors.affiliation: Sydney Emerging Infectious and Biosecurity Institute, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: edward.holmes@sydney.edu.au.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos-Universidade do Porto/InBIO, Laboratório Associado, Vairão, Portugal; Departamento de Biologia, Faculdade de Ciências da Universidade do Porto, Porto, Portugal; CITS, Centro de Investigação em Tecnologias da Saúde, IPSN, CESPU, Gandra, Portugal. Electronic address: pjesteves@cibio.up.pt.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Esteves
authors.affiliation: CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos-Universidade do Porto/InBIO, Laboratório Associado, Vairão, Portugal. Electronic address: jabrantes@cibio.up.pt.
authors.forename: Joana
authors.initials: J
authors.lastname: Abrantes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D002044:Bunyaviridae Infections / Q000453:epidemiology / Q000662:veterinary / Q000821:virology; D000939:Epitopes / Q000235:genetics; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D014644:Genetic Variation; D034621:Hares / Q000821:virology; D029321:Lagovirus / Q000235:genetics*; D008099:Liver / Q000821:virology; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes
keywords: Antigenic variation; European brown hare syndrome virus (EBHSV); Evolution