title: Reassortment between Avian H5N1 and human influenza viruses is mainly restricted to the matrix and neuraminidase gene segments.
abstract: Highly pathogenic avian influenza H5N1 viruses have devastated the poultry industry in many countries of the eastern hemisphere. Occasionally H5N1 viruses cross the species barrier and infect humans, sometimes with a severe clinical outcome. When this happens, there is a chance of reassortment between H5N1 and human influenza viruses. To assess the potential of H5N1 viruses to reassort with contemporary human influenza viruses (H1N1, H3N2 and pandemic H1N1), we used an in vitro selection method to generate reassortant viruses, that contained the H5 hemagglutinin gene, and that have a replication advantage in vitro. We found that the neuraminidase and matrix gene segments of human influenza viruses were preferentially selected by H5 viruses. However, these H5 reassortant viruses did not show a marked increase in replication in MDCK cells and human bronchial epithelial cells. In ferrets, inoculation with a mixture of H5N1-pandemic H1N1 reassortant viruses resulted in outgrowth of reassortant H5 viruses that had incorporated the neuraminidase and matrix gene segment of pandemic 2009 H1N1. This virus was not transmitted via aerosols or respiratory droplets to naïve recipient ferrets. Altogether, these data emphasize the potential of avian H5N1 viruses to reassort with contemporary human influenza viruses. The neuraminidase and matrix gene segments of human influenza viruses showed the highest genetic compatibility with HPAI H5N1 virus.
authors.affiliation: Viroscience Lab, Postgraduate School Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Eefje J A
authors.initials: EJ
authors.lastname: Schrauwen
authors.forename: Theo M
authors.initials: TM
authors.lastname: Bestebroer
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Sander
authors.initials: S
authors.lastname: Herfst
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D005289:Ferrets; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000635:transmission / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011200:Poultry; D016865:Reassortant Viruses / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014763:Viral Matrix Proteins / Q000235:genetics; D015047:Zoonoses / Q000821:virology*
chemical_list: D017931:DNA Primers; D014763:Viral Matrix Proteins; D009439:Neuraminidase