Virulence differences of closely related pandemic 2009 H1N1 isolates correlate with increased inflammatory responses in ferrets

Isabelle Meunier, Carissa Embury-Hyatt, Shane Stebner, Michael Gray, Nathalie Bastien, Yan Li, Francis Plummer, Gary P. Kobinger, Veronika Von Messling

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Several early pandemic H1N1 influenza isolates cause severe disease in different animals models, while most strains result in mild clinical signs similar to seasonal influenza. In this study, the pathogenesis of the virulent Mexican isolate A/Mexico/InDRE4487/2009 and a mild Canadian isolate A/Canada-AB/RV1532/2009 was compared in ferrets. These viruses differed at nine residues, none of which has been previously identified as virulence factor. The Mexican isolate caused more severe disease and higher mortality, and reached higher peak nasal wash titers. Both viruses grew similarly in the respiratory tract, but only the virulent virus was detected in the gut after day 3. During the acute phase, both strains caused similar lung pathology, however the Mexican isolate induced severe inflammation even after virus clearance. This virus was also associated with a rapid and sustained induction of inflammatory cytokines, indicating that early dysregulation of the host response contributes importantly to the disease outcome.

Original languageEnglish (US)
Pages (from-to)125-131
Number of pages7
JournalVirology
Volume422
Issue number1
DOIs
StatePublished - Jan 5 2012
Externally publishedYes

Keywords

  • Ferret model
  • H1N1 2009 pandemic influenza
  • Histopathological differences
  • Inflammatory host response profile
  • Mild and severe strains
  • Pathogenesis comparison

ASJC Scopus subject areas

  • Virology

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