title: Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.
abstract: Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Judith M A
authors.initials: JM
authors.lastname: van den Brand
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wohlsein
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Herfst
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Bodewes
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Pfankuche
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Marco W G
authors.initials: MW
authors.lastname: van de Bildt
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Seehusen
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Puff
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Richard
authors.affiliation: Institute for Terrestrial and Aquatic Wildlife Research (ITAW), University of Veterinary Medicine Hannover, Werftstraβe 6, D-25761, Büsum, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Siebert
authors.affiliation: Institute for Terrestrial and Aquatic Wildlife Research (ITAW), University of Veterinary Medicine Hannover, Werftstraβe 6, D-25761, Büsum, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lehnert
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Bestebroer
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lexmond
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.affiliation: Institute for Hygiene and Infectious Diseases of Animals, Justus-Liebig-University, Frankfurter Straβe 85-89, 35392, Giessen, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Prenger-Berninghoff
authors.affiliation: Institute for Hygiene and Infectious Diseases of Animals, Justus-Liebig-University, Frankfurter Straβe 85-89, 35392, Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Herbst
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Koopmans
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.|Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
mesh_terms: D000820:Animal Diseases / Q000473:pathology / Q000821:virology; D000818:Animals; D005260:Female; D005289:Ferrets / Q000821:virology*; D057921:Influenza A Virus, H10N7 Subtype / Q000302:isolation & purification; D008297:Male; D009976:Orthomyxoviridae Infections / Q000662:veterinary*; D046049:Phoca / Q000821:virology*; D020545:Respiratory Mucosa / Q000473:pathology / Q000648:ultrastructure / Q000821:virology; D012140:Respiratory Tract Diseases / Q000662:veterinary*