title: Virus replication kinetics and pathogenesis of infection with H7N9 influenza virus in isogenic guinea pigs upon intratracheal inoculation.
abstract: Since 2013, avian influenza viruses of subtype H7N9 have been transmitted from poultry to humans in China and caused severe disease. Concerns persist over the pandemic potential of this virus and further understanding of immunity and transmission is required. The isogenic guinea pig model uniquely would allow for investigation into both. Eighteen female isogenic guinea pigs 12-16 weeks were inoculated intratracheally with either A/H7N9 virus (n=12) or PBS (n=6) and sacrificed on days 2 and 7 post-inoculation. Nasal and pharyngeal swabs were taken daily to assess viral replication kinetics and necropsies were performed to study pathogenesis. All animals showed peak virus titers in nasal secretions at day 2 post-inoculation and by day 7 post-inoculation infectious virus titers had decreased to just above detectable levels. At day 2, high virus titers were found in nasal turbinates and lungs and moderate titers in trachea and cerebrum. At day 7, infectious virus was detected in the nasal turbinates only. Histology showed moderate to severe inflammation in the entire respiratory tract and immunohistochemistry (IHC) demonstrated large numbers of viral antigen positive cells in the nasal epithelium at day 2 and fewer at day 7 post-inoculation. A moderate number of IHC positive cells was observed in the bronchi(oli) and alveoli at day 2 only. This study indicates that isogenic guinea pigs are a promising model to further study immunity to and transmission of H7N9 influenza virus.
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Lidewij C M
authors: LC
authors: Wiersma
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Joost H C M
authors: JH
authors: Kreijtz
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Stella E
authors: SE
authors: Vogelzang-van Trierum
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; Viroclinics Biosciences B.V., Rotterdam Science Tower, Marconistraat 16, 3029 AK Rotterdam, The Netherlands.
authors: Geert
authors: G
authors: van Amerongen
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Peter
authors: P
authors: van Run
authors: Department of Experimental Toxicology and Centre for Documentation and Evaluation of Alternatives to Animal Experiments, The Federal Institute for Risk Assessment, Diedersdorfer Weg 1, 12277 Berlin, Germany.
authors: Mechtild
authors: M
authors: Ladwig
authors: Department of Experimental Toxicology and Centre for Documentation and Evaluation of Alternatives to Animal Experiments, The Federal Institute for Risk Assessment, Diedersdorfer Weg 1, 12277 Berlin, Germany.
authors: Stefanie
authors: S
authors: Banneke
authors: Division 16, Mycotic and Parasitic Agents and Mycobacteria, Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany.
authors: Hubert
authors: H
authors: Schaefer
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Ron A M
authors: RA
authors: Fouchier
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Thijs
authors: T
authors: Kuiken
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; Viroclinics Biosciences B.V., Rotterdam Science Tower, Marconistraat 16, 3029 AK Rotterdam, The Netherlands.
authors: Albert D M E
authors: AD
authors: Osterhaus
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; Viroclinics Biosciences B.V., Rotterdam Science Tower, Marconistraat 16, 3029 AK Rotterdam, The Netherlands. Electronic address: g.rimmelzwaan@erasmusmc.nl.
authors: Guus F
authors: GF
authors: Rimmelzwaan
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D005260:Female; D006168:Guinea Pigs; D064766:Influenza A Virus, H7N9 Subtype / Q000472:pathogenicity / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D009297:Nasal Mucosa / Q000473:pathology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000821:virology*; D014132:Trachea / Q000473:pathology / Q000821:virology; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral
keywords: Animal model; H7N9; Influenza; Isogenic guinea pig; Pathogenesis