Modeling host responses in ferrets during A/California/07/2009 influenza infection

Virology. 2010 Jun 5;401(2):257-65. doi: 10.1016/j.virol.2010.02.020. Epub 2010 Mar 23.


Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Cytokines / biosynthesis
  • Ferrets
  • Gene Expression Profiling
  • Histocytochemistry
  • Immunohistochemistry
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Lung / pathology
  • Male
  • Microscopy
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology*
  • Orthomyxoviridae Infections / virology
  • Time Factors


  • Antibodies, Viral
  • Cytokines