H5N1 hybrid viruses bearing 2009/H1N1 virus genes transmit in guinea pigs by respiratory droplet

Science. 2013 Jun 21;340(6139):1459-63. doi: 10.1126/science.1229455. Epub 2013 May 2.


In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies showed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / virology
  • Cell Line
  • Ferrets
  • Genes, Viral
  • Guinea Pigs
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / pathogenicity
  • Influenza A Virus, H5N1 Subtype / genetics*
  • Influenza A Virus, H5N1 Subtype / pathogenicity
  • Influenza, Human / transmission
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Mutation
  • Orthomyxoviridae Infections / transmission*
  • Orthomyxoviridae Infections / virology*
  • Reassortant Viruses / genetics*
  • Reassortant Viruses / pathogenicity*
  • Receptors, Cell Surface / metabolism
  • Receptors, Virus / metabolism
  • Respiratory System / virology*
  • Reverse Genetics
  • Ribonucleoproteins / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Cell Surface
  • Receptors, Virus
  • Ribonucleoproteins
  • Viral Proteins
  • hemagglutinin, avian influenza A virus
  • sialic acid receptor