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Journal of virology2015; 89(13); 6860-6873; doi: 10.1128/JVI.00521-15

Equine and Canine Influenza H3N8 Viruses Show Minimal Biological Differences Despite Phylogenetic Divergence.

Abstract: The A/H3N8 canine influenza virus (CIV) emerged from A/H3N8 equine influenza virus (EIV) around the year 2000 through the transfer of a single virus from horses to dogs. We defined and compared the biological properties of EIV and CIV by examining their genetic variation, infection, and growth in different cell cultures, receptor specificity, hemagglutinin (HA) cleavage, and infection and growth in horse and dog tracheal explant cultures. Comparison of sequences of viruses from horses and dogs revealed mutations that may be linked to host adaptation and tropism. We prepared infectious clones of representative EIV and CIV strains that were similar to the consensus sequences of viruses from each host. The rescued viruses, including HA and neuraminidase (NA) double reassortants, exhibited similar degrees of long-term growth in MDCK cells. Different host cells showed various levels of susceptibility to infection, but no differences in infectivity were seen when comparing viruses. All viruses preferred α2-3- over α2-6-linked sialic acids for infections, and glycan microarray analysis showed that EIV and CIV HA-Fc fusion proteins bound only to α2-3-linked sialic acids. Cleavage assays showed that EIV and CIV HA proteins required trypsin for efficient cleavage, and no differences in cleavage efficiency were seen. Inoculation of the viruses into tracheal explants revealed similar levels of infection and replication by each virus in dog trachea, although EIV was more infectious in horse trachea than CIV. Objective: Influenza A viruses can cross species barriers and cause severe disease in their new hosts. Infections with highly pathogenic avian H5N1 virus and, more recently, avian H7N9 virus have resulted in high rates of lethality in humans. Unfortunately, our current understanding of how influenza viruses jump species barriers is limited. Our aim was to provide an overview and biological characterization of H3N8 equine and canine influenza viruses using various experimental approaches, since the canine virus emerged from horses approximately 15 years ago. We showed that although there were numerous genetic differences between the equine and canine viruses, this variation did not result in dramatic biological differences between the viruses from the two hosts, and the viruses appeared phenotypically equivalent in most assays we conducted. These findings suggest that the cross-species transmission and adaptation of influenza viruses may be mediated by subtle changes in virus biology.
Publication Date: 2015-04-22 PubMed ID: 25903329PubMed Central: PMC4468500DOI: 10.1128/JVI.00521-15Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

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.

The research focuses on comparing the biological properties of the A/H3N8 canine influenza virus (CIV) and A/H3N8 equine influenza virus (EIV), both of which are strains of the influenza A virus. Despite genetic variations, the viruses showed minor biological differences which the study suggests might be indicative of how influenza viruses cross species barriers.

Methodology

  • The comparative study involved an examination of the genetic variation, infection and growth of the EIV and CIV strains in different cell cultures.
  • The specificity of receptors, the process of hemagglutinin cleavage, and the viruses’ ability to infect and grow in horse and dog tracheal explant cultures were also investigated.
  • To further compare the viruses, the scientists prepared infectious clones that were similar to the consensus sequences of the viruses from each host.
  • In addition, glycan microarray analysis was used to gauge whether the EIV and CIV Hemagglutinin fusion proteins had a preference for α2-3- or α2-6-linked sialic acids.

Findings

  • The scientists discovered mutations in the sequences of the viruses from horses and dogs that might play a role in host adaptation and tropism.
  • Contrary to expectations, no significant differences in long-term growth were observed in the MDCK cells infected with the cloned viruses.
  • Examination of different host cells revealed various susceptibility levels to infection, but comparably, the viruses did not show any infectivity differences.
  • The glycan microarray analysis demonstrated that both EIV and CIV had a preference for α2-3- linked sialic acids.
  • It was also found that both the EIV and CIV Hemagglutinin proteins required trypsin for efficient cleavage, and no notable differences were noticed in the efficiency of this process.
  • Both EIV and CIV demonstrated similar infection and replication levels in dog trachea, however, EIV was more infectious in horse trachea than CIV.

Conclusion

  • While there were quite a few genetic variations between the equine and canine viruses, these variations did not bring about significant biological differences in the viruses.
  • Based on these analyses and comparisons, the study concludes that the cross-species transmission and adaptation of influenza viruses might be guided by subdued changes in viral biology, a conclusion that can contribute to further understanding of how influenza viruses jump species barriers and the resulting occasional severity of their impact in the new hosts.

Cite This Article

APA
Feng KH, Gonzalez G, Deng L, Yu H, Tse VL, Huang L, Huang K, Wasik BR, Zhou B, Wentworth DE, Holmes EC, Chen X, Varki A, Murcia PR, Parrish CR. (2015). Equine and Canine Influenza H3N8 Viruses Show Minimal Biological Differences Despite Phylogenetic Divergence. J Virol, 89(13), 6860-6873. https://doi.org/10.1128/JVI.00521-15

Publication

ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 89
Issue: 13
Pages: 6860-6873

Researcher Affiliations

Feng, Kurtis H
  • Department of Microbiology and Immunology, Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Gonzalez, Gaelle
  • Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom.
Deng, Lingquan
  • Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California, USA.
Yu, Hai
  • Department of Chemistry, University of California, Davis, Davis, California, USA.
Tse, Victor L
  • Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Huang, Lu
  • Department of Microbiology and Immunology, Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Huang, Kai
  • Department of Microbiology and Immunology, Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Wasik, Brian R
  • Department of Microbiology and Immunology, Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Zhou, Bin
  • Infectious Disease Group, J. Craig Venter Institute, Rockville, Maryland, USA.
Wentworth, David E
  • Infectious Disease Group, J. Craig Venter Institute, Rockville, Maryland, USA.
Holmes, Edward C
  • Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Chen, Xi
  • Department of Chemistry, University of California, Davis, Davis, California, USA.
Varki, Ajit
  • Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California, USA.
Murcia, Pablo R
  • Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom.
Parrish, Colin R
  • Department of Microbiology and Immunology, Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA crp3@cornell.edu.

MeSH Terms

  • Adaptation, Biological
  • Animals
  • Cell Line
  • Dogs
  • Genetic Variation
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Horses
  • Influenza A Virus, H3N8 Subtype / genetics
  • Influenza A Virus, H3N8 Subtype / growth & development
  • Influenza A Virus, H3N8 Subtype / isolation & purification
  • Influenza A Virus, H3N8 Subtype / physiology
  • Mutation
  • Phylogeny
  • Protein Binding
  • Receptors, Virus / metabolism
  • Sialic Acids / metabolism
  • Trachea / virology
  • Viral Tropism
  • Virus Attachment

Grant Funding

  • G0801822 / Medical Research Council
  • R01 GM032373 / NIGMS NIH HHS
  • R01 GM080533 / NIGMS NIH HHS
  • R01GM32373 / NIGMS NIH HHS

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