title: Spatiotemporal Analysis of the Genetic Diversity of Seal Influenza A(H10N7) Virus, Northwestern Europe.
abstract: Influenza A viruses are major pathogens for humans, domestic animals, and wildlife, and these viruses occasionally cross the species barrier. In spring 2014, increased mortality of harbor seals (Phoca vitulina), associated with infection with an influenza A(H10N7) virus, was reported in Sweden and Denmark. Within a few months, this virus spread to seals of the coastal waters of Germany and the Netherlands, causing the death of thousands of animals. Genetic analysis of the hemagglutinin (HA) and neuraminidase (NA) genes of this seal influenza A(H10N7) virus revealed that it was most closely related to various avian influenza A(H10N7) viruses. The collection of samples from infected seals during the course of the outbreak provided a unique opportunity to follow the adaptation of the avian virus to its new seal host. Sequence data for samples collected from 41 different seals from four different countries between April 2014 and January 2015 were obtained by Sanger sequencing and next-generation sequencing to describe the molecular epidemiology of the seal influenza A(H10N7) virus. The majority of sequence variation occurred in the HA gene, and some mutations corresponded to amino acid changes not found in H10 viruses isolated from Eurasian birds. Also, sequence variation in the HA gene was greater at the beginning than at the end of the epidemic, when a number of the mutations observed earlier had been fixed. These results imply that when an avian influenza virus jumps the species barrier from birds to seals, amino acid changes in HA may occur rapidly and are important for virus adaptation to its new mammalian host.
  
  
  OBJECTIVE
  Influenza A viruses are major pathogens for humans, domestic animals, and wildlife. In addition to the continuous circulation of influenza A viruses among various host species, cross-species transmission of influenza A viruses occurs occasionally. Wild waterfowl and shorebirds are the main reservoir for most influenza A virus subtypes, and spillover of influenza A viruses from birds to humans or other mammalian species may result in major outbreaks. In the present study, various sequencing methods were used to elucidate the genetic changes that occurred after the introduction and subsequent spread of an avian influenza A(H10N7) virus among harbor seals of northwestern Europe by use of various samples collected during the outbreak. Such detailed knowledge of genetic changes necessary for introduction and adaptation of avian influenza A viruses to mammalian hosts is important for a rapid risk assessment of such viruses soon after they cross the species barrier.
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands rogier.bodewes@gmail.com.
authors.forename: Rogier
authors.initials: R
authors.lastname: Bodewes
authors.affiliation: Department of Virology, Immunobiology and Parasitology, National Veterinary Institute, Uppsala, Sweden.
authors.forename: Siamak
authors.initials: S
authors.lastname: Zohari
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: Jesper S
authors.initials: JS
authors.lastname: Krog
authors.affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hall
authors.affiliation: Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Greifswald Insel-Riems, Germany.
authors.forename: Timm C
authors.initials: TC
authors.lastname: Harder
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Bestebroer
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Marco W G
authors.initials: MWG
authors.lastname: van de Bildt
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Monique I
authors.initials: MI
authors.lastname: Spronken
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: Lars E
authors.initials: LE
authors.lastname: Larsen
authors.affiliation: Institute for Terrestrial and Aquatic Wildlife Research, University of Veterinary Medicine Hannover, Büsum, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Siebert
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wohlsein
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Puff
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Seehusen
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Department of Environmental Research and Monitoring, Swedish Museum of Natural History, Stockholm, Sweden.
authors.forename: Tero
authors.initials: T
authors.lastname: Härkönen
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Saskia L
authors.initials: SL
authors.lastname: Smits
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Herfst
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.|Artemis One Health, Utrecht, the Netherlands.|Research Centre for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Albert D M E
authors.initials: ADME
authors.lastname: Osterhaus
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Ron A M
authors.initials: RAM
authors.lastname: Fouchier
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.|National Institute of Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, the Netherlands.
authors.forename: Marion P
authors.initials: MP
authors.lastname: Koopmans
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019295:Computational Biology / Q000379:methods; D005060:Europe / Q000453:epidemiology; D014644:Genetic Variation; D016679:Genome, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D057921:Influenza A Virus, H10N7 Subtype / Q000145:classification / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000453:epidemiology* / Q000821:virology*; D046049:Phoca / Q000821:virology*; D010802:Phylogeny; D058974:Phylogeography; D062211:Spatio-Temporal Analysis
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus
references.citation: Mol Biol Evol. 1999 Jan;16(1):37-48
references.pmid: 10331250
references.citation: J Mol Evol. 1985;22(2):160-74
references.pmid: 3934395
references.citation: PLoS One. 2013 May 15;8(5):e62259
references.pmid: 23690933
references.citation: Ecohealth. 2016 Mar;13(1):161-70
references.pmid: 25231137
references.citation: Mol Biol Evol. 2013 Mar;30(3):713-24
references.pmid: 23180580
references.citation: Mol Biol Evol. 2012 Aug;29(8):1969-73
references.pmid: 22367748
references.citation: Emerg Infect Dis. 2015 Apr;21(4):720-2
references.pmid: 25811303
references.citation: One Health. 2015 Dec 1;1:1-13
references.pmid: 26309905
references.citation: Ecohealth. 2016 Mar;13(1):171-98
references.pmid: 25630935
references.citation: Emerg Infect Dis. 2012 May;18(5):817-20
references.pmid: 22516350
references.citation: Mol Biol Evol. 2013 Dec;30(12):2725-9
references.pmid: 24132122
references.citation: Arch Virol. 2001 Dec;146(12):2275-89
references.pmid: 11811679
references.citation: mBio. 2012 Jul 31;3(4):e00166-12
references.pmid: 22851656
references.citation: Microbiol Rev. 1992 Mar;56(1):152-79
references.pmid: 1579108
references.citation: Cell. 2014 Apr 10;157(2):329-339
references.pmid: 24725402
references.citation: Emerg Infect Dis. 2015 Apr;21(4):684-7
references.pmid: 25811098
references.citation: Am J Pathol. 2007 Oct;171(4):1215-23
references.pmid: 17717141
references.citation: Virology. 1981 Sep;113(2):712-24
references.pmid: 6267805
references.citation: J Virol Methods. 1998 Sep;74(1):57-66
references.pmid: 9763129
references.citation: Euro Surveill. 2014 Nov 20;19(46):
references.pmid: 25425511
references.citation: PLoS Biol. 2006 May;4(5):e88
references.pmid: 16683862
references.citation: J Gen Virol. 1995 Jan;76 ( Pt 1):199-203
references.pmid: 7844533