Origins and Evolutionary Dynamics of H3N2 Canine Influenza Virus

J Virol. 2015 May;89(10):5406-18. doi: 10.1128/JVI.03395-14. Epub 2015 Mar 4.


Influenza A viruses (IAVs) are maintained mainly in wild birds, and despite frequent spillover infections of avian IAVs into mammals, only a small number of viruses have become established in mammalian hosts. A new H3N2 canine influenza virus (CIV) of avian origin emerged in Asia in the mid-2000s and is now circulating in dog populations of China and South Korea, and possibly in Thailand. The emergence of CIV provides new opportunities for zoonotic infections and interspecies transmission. We examined 14,764 complete IAV genomes together with all CIV genomes publicly available since its first isolation until 2013. We show that CIV may have originated as early as 1999 as a result of segment reassortment among Eurasian and North American avian IAV lineages. We also identified amino acid changes that might have played a role in CIV emergence, some of which have not been previously identified in other cross-species jumps. CIV evolves at a lower rate than H3N2 human influenza viruses do, and viral phylogenies exhibit geographical structure compatible with high levels of local transmission. We detected multiple intrasubtypic and heterosubtypic reassortment events, including the acquisition of the NS segment of an H5N1 avian influenza virus that had previously been overlooked. In sum, our results provide insight into the adaptive changes required by avian viruses to establish themselves in mammals and also highlight the potential role of dogs to act as intermediate hosts in which viruses with zoonotic and/or pandemic potential could originate, particularly with an estimated dog population of ∼ 700 million.

Importance: Influenza A viruses circulate in humans and animals. This multihost ecology has important implications, as past pandemics were caused by IAVs carrying gene segments of both human and animal origin. Adaptive evolution is central to cross-species jumps, and this is why understanding the evolutionary processes that shape influenza A virus genomes is key to elucidating the mechanisms underpinning viral emergence. An avian-origin canine influenza virus (CIV) has recently emerged in dogs and is spreading in Asia. We reconstructed the evolutionary history of CIV and show that it originated from both Eurasian and North American avian lineages. We also identified the mutations that might have been responsible for the cross-species jump. Finally, we provide evidence of multiple reassortment events between CIV and other influenza viruses (including an H5N1 avian virus). This is a cause for concern, as there is a large global dog population to which humans are highly exposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Birds
  • Databases, Genetic
  • Dog Diseases / virology*
  • Dogs
  • Evolution, Molecular
  • Genome, Viral
  • Host Specificity
  • Humans
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza A Virus, H3N2 Subtype / isolation & purification
  • Influenza A Virus, H3N2 Subtype / pathogenicity
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / isolation & purification
  • Influenza A Virus, H5N1 Subtype / pathogenicity
  • Influenza in Birds / virology*
  • Influenza, Human / virology
  • Mutation
  • Orthomyxoviridae Infections / veterinary*
  • Orthomyxoviridae Infections / virology
  • Phylogeny
  • Reassortant Viruses / genetics
  • Reassortant Viruses / isolation & purification
  • Reassortant Viruses / pathogenicity
  • Selection, Genetic
  • Time Factors
  • Viral Proteins / genetics


  • Viral Proteins