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Journal of virology2014; 88(16); 9208-9219; doi: 10.1128/JVI.00887-14

Infection and pathogenesis of canine, equine, and human influenza viruses in canine tracheas.

Abstract: Influenza A viruses (IAVs) can jump species barriers and occasionally cause epidemics, epizootics, pandemics, and panzootics. Characterizing the infection dynamics at the target tissues of natural hosts is central to understanding the mechanisms that control host range, tropism, and virulence. Canine influenza virus (CIV; H3N8) originated after the transfer of an equine influenza virus (EIV) into dogs. Thus, comparing CIV and EIV isolates provides an opportunity to study the determinants of influenza virus emergence. Here we characterize the replication of canine, equine, and human IAVs in the trachea of the dog, a species to which humans are heavily exposed. We define a phenotype of infection for CIV, which is characterized by high levels of virus replication and extensive tissue damage. CIV was compared to evolutionarily distinct EIVs, and the early EIV isolates showed an impaired ability to infect dog tracheas, while EIVs that circulated near the time of CIV emergence exhibited a CIV-like infection phenotype. Inoculating dog tracheas with various human IAVs (hIAVs) showed that they infected the tracheal epithelium with various efficiencies depending on the virus tested. Finally, we show that reassortant viruses carrying gene segments of CIV and hIAV are viable and that addition of the hemagglutinin (HA) and neuraminidase (NA) of CIV to the 2009 human pandemic virus results in a virus that replicates at high levels and causes significant lesions. This provides important insights into the role of evolution on viral emergence and on the role of HA and NA as determinants of pathogenicity. Objective: Influenza A viruses (IAVs) have entered new host species in recent history, sometimes with devastating consequences. Canine influenza virus (CIV) H3N8 originated from a direct transfer of an equine influenza virus (EIV) in the early 2000s. We studied the infection patterns of IAVs that circulate in dogs or to which dogs are commonly exposed and showed that CIV emergence was likely caused by an adaptive driver, as evolutionarily distinct EIVs display distinct infection phenotypes. We also showed that many human viruses can infect dog tracheas and that reassortment with CIV results in viable viruses. Finally, we showed that the hemagglutinin and neuraminidase of CIV act as virulence factors. Our findings have significant implications because they show that dogs might act as "mixing vessels" in which novel viruses with pandemic potential could emerge and also provide experimental evidence supporting the role of viral evolution in influenza virus emergence.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Publication Date: 2014-06-04 PubMed ID: 24899186PubMed Central: PMC4136294DOI: 10.1128/JVI.00887-14Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research is about how Influenza A viruses (IAVs), including canine, equine, and human strains, infected and caused disease in the tracheas of dogs. By comparing these strains, the researchers aimed to understand the factors that contribute to the emergence of influenza viruses and virulence factors.

Understanding the Infection Dynamics

  • The study centered on characterizing the infection dynamics in canine tracheas, a common species exposed to humans, using different forms of Influenza A viruses (IAVs) – those that occur in canines (CIV), equines (EIV), and humans (hIAVs).
  • The research found that CIV, originally developed from a transfer of equine influenza virus (EIV) to dogs, resulted in high levels of virus replication and extensive tissue damage, describing it as a “phenotype of infection”.
  • Different EIV strains showed varied abilities to infect canine tracheas. Earlier strains of EIV had limited ability to infect dog tracheas, while strains circulating around the time CIV emerged displayed a similar infection pattern to CIV.

The Role of Human Influenza Viruses

  • The scientists also studied the ability of human IAVs to cause infection in dog tracheas. They found varying degrees of infection efficiency depending on the human virus strain.
  • Another important discovery was that reassortant viruses containing gene segments from CIV and hIAV could replicate. A hybrid virus, combining the hemagglutinin and neuraminidase from CIV with the 2009 human pandemic virus, demonstrated high replication levels and significant tissue damage.

Bigger Implications

  • The research highlighted the role of evolution in determining the emergence of a virus, essentially showing that evolutionarily distinct EIVs had distinctive infection phenotypes.
  • The results suggested that dogs could possibly serve as “mixing vessels” for novel viruses with pandemic potential. This was shown by the successful replication of reassortant viruses combining elements of CIV and human IAV.
  • Researchers established the hemagglutinin and neuraminidase of CIV as significant factors in virulence, indicating the role of viral evolution in influenza virus emergence.

In summary, the study provides insights into influenza virus emergence, virulence and the role of different species in these processes. This could prove vital in monitoring and preventing future flu pandemics.

Cite This Article

APA
Gonzalez G, Marshall JF, Morrell J, Robb D, McCauley JW, Perez DR, Parrish CR, Murcia PR. (2014). Infection and pathogenesis of canine, equine, and human influenza viruses in canine tracheas. J Virol, 88(16), 9208-9219. https://doi.org/10.1128/JVI.00887-14

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 88
Issue: 16
Pages: 9208-9219

Researcher Affiliations

Gonzalez, Gaelle
  • MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Marshall, John F
  • Weipers Centre Equine Hospital, School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.
Morrell, Joanna
  • MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Robb, David
  • Charles River Laboratories Preclinical Services, Tranent, United Kingdom.
McCauley, John W
  • Division of Virology, Medical Research Council, National Institute for Medical Research, London, United Kingdom.
Perez, Daniel R
  • Virginia-Maryland Regional College of Veterinary Medicine, Department of Veterinary Medicine, University of Maryland, Maryland, USA.
Parrish, Colin R
  • Baker Institute of Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, USA.
Murcia, Pablo R
  • MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom Pablo.Murcia@Glasgow.ac.uk.

MeSH Terms

  • Animals
  • Dog Diseases / metabolism
  • Dog Diseases / virology
  • Dogs
  • Hemagglutinins / metabolism
  • Horses / virology
  • Host Specificity
  • Humans
  • Influenza A Virus, H3N8 Subtype / pathogenicity
  • Influenza, Human / virology
  • Neuraminidase / metabolism
  • Orthomyxoviridae Infections / metabolism
  • Orthomyxoviridae Infections / virology
  • Reassortant Viruses / pathogenicity
  • Respiratory Mucosa / virology
  • Trachea / metabolism
  • Trachea / virology
  • Virus Replication

Grant Funding

  • 2 R01 GM080533 / NIGMS NIH HHS
  • MC_U117512723 / Medical Research Council
  • U117512723 / Medical Research Council
  • R01 GM080533 / NIGMS NIH HHS
  • G0801822 / Medical Research Council

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Citations

This article has been cited 27 times.
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