Pathogenesis of Infection with 2009 Pandemic H1N1 Influenza Virus in Isogenic Guinea Pigs after Intranasal or Intratracheal Inoculation

Lidewij Wiersma, Stella Trierum, Geert Amerongen, Peter van Run, Nella Nieuwkoop, M Ladwig, S Banneke, H Schaefer, Thijs Kuiken, Ron Fouchier, Ab Osterhaus, Guus Rimmelzwaan

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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.
Original languageUndefined/Unknown
Pages (from-to)643-650
Number of pages8
JournalAmerican Journal of Pathology
Volume185
Issue number3
DOIs
Publication statusPublished - 2015

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  • EMC MM-04-27-01

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