title: Pathogenesis of infection with 2009 pandemic H1N1 influenza virus in isogenic guinea pigs after intranasal or intratracheal inoculation.
abstract: To elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. To investigate protective immune responses, the use of inbred mouse strains has proven invaluable. Here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. Strain 2 isogenic guinea pigs were inoculated with H1N1pdm09 influenza virus A/Netherlands/602/09 by the intranasal or intratracheal route. Viral replication kinetics were assessed by determining virus titers in nasal swabs and respiratory tissues, which were also used to assess histopathologic changes and the number of infected cells. In all guinea pigs, virus titers peaked in nasal secretions at day 2 after inoculation. Intranasal inoculation resulted in higher virus excretion via the nose and higher virus titers in the nasal turbinates than intratracheal inoculation. After intranasal inoculation, infectious virus was recovered only from nasal epithelium; after intratracheal inoculation, it was recovered also from trachea, lung, and cerebrum. Histopathologic changes corresponded with virus antigen distribution, being largely limited to nasal epithelium for intranasally infected guinea pigs and more widespread in the respiratory tract for intratracheally infected guinea pigs. In summary, isogenic guinea pigs show promise as a model to investigate the role of humoral and cell-mediated immunities to influenza and their effect on virus transmission.
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Lidewij C M
authors.initials: LC
authors.lastname: Wiersma
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Vogelzang-van Trierum
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands; Viroclinics Biosciences BV, Rotterdam, the Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van Run
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Nella J
authors.initials: NJ
authors.lastname: Nieuwkoop
authors.affiliation: Department of Experimental Toxicology and Centre for Documentation and Evaluation of Alternatives to Animal Experiments, the Federal Institute for Risk Assessment, Berlin, Germany.
authors.forename: Mechtild
authors.initials: M
authors.lastname: Ladwig
authors.affiliation: Department of Experimental Toxicology and Centre for Documentation and Evaluation of Alternatives to Animal Experiments, the Federal Institute for Risk Assessment, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Banneke
authors.affiliation: Experimental Immunology, the Robert Koch Institute, Berlin, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schaefer
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands; Viroclinics Biosciences BV, Rotterdam, the Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Viroscience Laboratory, Erasmus Medical Centre, Rotterdam, the Netherlands; Viroclinics Biosciences BV, Rotterdam, the Netherlands. Electronic address: g.rimmelzwaan@erasmusmc.nl.
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D006168:Guinea Pigs; D007111:Immunity, Cellular / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype; D008168:Lung / Q000276:immunology / Q000473:pathology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000635:transmission; D014132:Trachea / Q000276:immunology / Q000473:pathology*; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral