A North American H7N3 influenza virus supports reassortment with 2009 pandemic H1N1 and induces disease in mice without prior adaptation

Graham D. Williams, Amelia K. Pinto, Brittany Doll, Adrianus C.M. Boon

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Reassortment between H5 or H9 subtype avian and mammalian influenza A viruses (IAV) can generate a novel virus that causes disease and transmits between mammals. Such information is currently not available for H7 subtype viruses. We evaluated the ability of a low-pathogenicity North American avian H7N3 virus (A/shorebird/Delaware/22/2006) to reassort with mammalian or avian viruses using a plasmid-based competition assay. In addition to genome segments derived from an avian H7N9 virus, the H7N3 virus reassorted efficiently with the PB2, NA, andMsegments from the 2009 pandemic H1N1 (PH1N1) virus. In vitro and in vivo evaluation of the H7N3:PH1N1 (7 + 1) reassortant viruses revealed that the PB2, NA, orMsegments from PH1N1 largely do not attenuate the H7N3 virus, whereas the PB1, PA, NP, or NS genome segments from PH1N1 do. Additionally, we assessed the functionality of the H7N3:PH1N1 7 + 1 reassortant viruses by measuring the inflammatory response in vivo. We found that infection with wild-type H7N3 resulted in increased inflammatory cytokine production relative to that seen with the PH1N1 strain and that the increase was further exacerbated by substitution of PH1N1 PB2 but not NA or M. Finally, we assessed if any adaptations occurred in the individually substituted segments after in vivo inoculation and found no mutations, suggesting that PH1N1 PB2, NA, and Mare genetically stable in the background of this H7N3 virus. Taking the data together, we demonstrate that a North American avian H7N3 IAV is genetically and functionally compatible with multiple gene segments from the 2009 pandemic influenza virus strain without prior adaptation.

Original languageEnglish
Pages (from-to)4796-4806
Number of pages11
JournalJournal of virology
Volume90
Issue number9
DOIs
StatePublished - May 1 2016

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