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Proceedings of the National Academy of Sciences of the United States of America2014; 111(30); 11175-11180; doi: 10.1073/pnas.1406606111

Recent evolution of equine influenza and the origin of canine influenza.

Abstract: In 2004 an hemagglutinin 3 neuraminidase 8 (H3N8) equine influenza virus was transmitted from horses to dogs in Florida and subsequently spread throughout the United States and to Europe. To understand the molecular basis of changes in the antigenicity of H3 hemagglutinins (HAs) that have occurred during virus evolution in horses, and to investigate the role of HA in the equine to canine cross-species transfer, we used X-ray crystallography to determine the structures of the HAs from two antigenically distinct equine viruses and from a canine virus. Structurally all three are very similar with the majority of amino acid sequence differences between the two equine HAs located on the virus membrane-distal molecular surface. HAs of canine viruses are distinct in containing a Trp-222 → Leu substitution in the receptor binding site that influences specificity for receptor analogs. In the fusion subdomain of canine and recent equine virus HAs a unique difference is observed by comparison with all other HAs examined to date. Analyses of site-specific mutant HAs indicate that a single amino acid substitution, Thr-30 → Ser, influences interactions between N-terminal and C-terminal regions of the subdomain that are important in the structural changes required for membrane fusion activity. Both structural modifications may have facilitated the transmission of H3N8 influenza from horses to dogs.
Publication Date: 2014-07-14 PubMed ID: 25024224PubMed Central: PMC4121831DOI: 10.1073/pnas.1406606111Google Scholar: Lookup
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Summary

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The study explores the evolution of equine influenza, a horse disease, and its crossover to dogs, resulting in a new strain of canine influenza. The researchers used X-ray crystallography to analyze molecular structures and identified specific structural changes in the virus that likely contributed to its ability to infect dogs.

Investigation into H3N8 Virus Evolution and Crossover

The focus of the research was on a specific instance of cross-species transmission. In 2004, an equine influenza virus known as H3N8 jumped from horses to dogs in Florida, then spread throughout the United States and to Europe. The researchers were interested in understanding the molecular changes that allowed this to happen.

  • They studied the antigenicity of H3 hemagglutinins (HAs), a protein on the surface of the virus, using X-ray crystallography to examine structural details.
  • They examined HAs from two distinct equine viruses and one canine virus, all of which proved similar in structure.
  • The team identified the majority of amino acid sequence differences between the equine HAs on the surface of the virus membrane, the part that comes into contact with the host’s cell.

Key Structural Modifications in the Virus

In their findings, the researchers noted some unique attributes of the canine virus HA that could have influenced the cross-species transmission.

  • The canine virus HA contains a specific Trp-222 → Leu substitution in the receptor binding site. This alteration influences the virus’s specificity for receptor analogs, or synthetic compounds that mimic the structure and function of natural biological receptors.
  • In the fusion subdomain of the HA, the part responsible for the virus merging with the host cell’s membrane, both the canine and recent equine virus HAs exhibited a unique difference compared to all other HAs examined so far.
  • The team showed that a single amino acid substitution, Thr-30 → Ser, influences interactions between the N-terminal and C-terminal regions of this fusion subdomain, which play a crucial role in the structural changes required for membrane fusion activities.

The researchers concluded that these two specific structural modifications could have contributed to the H3N8 influenza virus’s ability to jump from horses to dogs, thus creating a new form of canine influenza.

Cite This Article

APA
Collins PJ, Vachieri SG, Haire LF, Ogrodowicz RW, Martin SR, Walker PA, Xiong X, Gamblin SJ, Skehel JJ. (2014). Recent evolution of equine influenza and the origin of canine influenza. Proc Natl Acad Sci U S A, 111(30), 11175-11180. https://doi.org/10.1073/pnas.1406606111

Publication

ISSN: 1091-6490
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 111
Issue: 30
Pages: 11175-11180

Researcher Affiliations

Collins, Patrick J
  • Divisions of Virology,Molecular Structure, and.
Vachieri, Sebastien G
  • Divisions of Virology,Molecular Structure, and.
Haire, Lesley F
  • Molecular Structure, and.
Ogrodowicz, Roksana W
  • Molecular Structure, and.
Martin, Stephen R
  • Physical Biochemistry, Medical Research Council, National Institute for Medical Research, London NW7 1AA, United Kingdom.
Walker, Philip A
  • Molecular Structure, and.
Xiong, Xiaoli
  • Divisions of Virology,Molecular Structure, and.
Gamblin, Steven J
  • Molecular Structure, and.
Skehel, John J
  • Divisions of Virology, skeheljj@nimr.mrc.ac.uk.

MeSH Terms

  • Amino Acid Substitution
  • Animals
  • Crystallography, X-Ray
  • Dog Diseases / genetics
  • Dog Diseases / metabolism
  • Dog Diseases / virology
  • Dogs
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Horse Diseases / genetics
  • Horse Diseases / metabolism
  • Horse Diseases / virology
  • Horses
  • Influenza A Virus, H3N8 Subtype / chemistry
  • Influenza A Virus, H3N8 Subtype / metabolism
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / metabolism
  • Protein Structure, Tertiary

Grant Funding

  • G0600522 / Medical Research Council
  • MC_U117584222 / Medical Research Council

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

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