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Virology2015; 481; 187-198; doi: 10.1016/j.virol.2015.02.027

Using epidemics to map H3 equine influenza virus determinants of antigenicity.

Abstract: Equine influenza is a major cause of respiratory infections in horses and causes widespread epidemics, despite the availability of commercial vaccines. Antigenic drift within the haemagglutinin (HA) glycoprotein is thought to play a part in vaccination breakdown. Here, we carried out a detailed investigation of the 1989 UK outbreak, using reverse genetics and site-directed mutagenesis, to determine the individual contribution of amino acid substitutions within HA. Mutations at positions 159, 189 and 227 all altered antigenicity, as measured by haemagglutination-inhibition assays. We also compared HA sequences for epidemic and vaccine strains from four epidemics and found that at least 8 amino acid differences were present, affecting multiple antigenic sites. Substitutions within antigenic site B and at least one other were associated with each outbreak, we also identified changes in loop regions close to antigenic sites that have not previously been highlighted for human H3 influenza viruses.
Publication Date: 2015-03-19 PubMed ID: 25797606DOI: 10.1016/j.virol.2015.02.027Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The researchers, in this study, have investigated the impact of specific changes in the glycoprotein haemagglutinin (HA) of the equine influenza virus on the effectiveness of vaccines. They found that particular mutations in the HA protein led to changes in the virus’s antigenicity, potentially contributing to the occurrence of global epidemics despite vaccination efforts.

Dissecting the Study

  • The main focus of the research was to understand the reason behind the recurrent epidemics of equine influenza, a prime cause of respiratory infections in horses, even with the presence of commercial vaccines. An existing hypothesis suggests that changes in the haemagglutinin (HA) glycoprotein, known as antigenic drift, might cause vaccines to become ineffective.
  • For a more nuanced understanding, the researchers delved into the details of the UK’s equine influenza outbreak in 1989. They used techniques called reverse genetics and site-directed mutagenesis, which can manipulate the genetic material of the virus to observe changes in its behavior.
  • The outcome of this intricate process revealed that changes or mutations at several positions (159, 189, and 227) within HA led to changes in the virus’s antigenicity, as assessed using haemagglutination-inhibition assays. Antigenicity refers to the ability of an antigen to bind with specific antibodies, a key process in triggering an immune response.

Comparative Study and Key Findings

  • In the next phase of the research, the team compared HA sequences from the virus strains involved in the epidemic and those used in vaccines from four different outbreaks. The comparison revealed a minimum of eight amino acid differences, affecting multiple antigenic sites.
  • Notably, the substitutions within antigenic site B and at least one other site were identified with every outbreak under study.
  • In addition to the known antigenic sites, the study also highlighted changes in the loop regions adjacent to these sites, something not previously emphasized for human H3 influenza viruses. These alterations might have roles in influencing the virus’s antigenicity and the associated immune response.
  • Overall, this study provides clear evidence that specific genetic mutations within the equine influenza virus can alter its antigenicity, potentially leading to vaccination failure and subsequent epidemics. This understanding could be significant in developing more effective vaccines in the future.

Cite This Article

APA
Woodward A, Rash AS, Medcalf E, Bryant NA, Elton DM. (2015). Using epidemics to map H3 equine influenza virus determinants of antigenicity. Virology, 481, 187-198. https://doi.org/10.1016/j.virol.2015.02.027

Publication

ISSN: 1096-0341
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 481
Pages: 187-198
PII: S0042-6822(15)00073-2

Researcher Affiliations

Woodward, Alana
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK. Electronic address: alana.woodward@aht.org.uk.
Rash, Adam S
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK. Electronic address: adam.rash@aht.org.uk.
Medcalf, Elizabeth
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK. Electronic address: elizabeth.medcalf@aht.org.uk.
Bryant, Neil A
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK. Electronic address: neil.bryant@aht.org.uk.
Elton, Debra M
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK. Electronic address: debra.elton@aht.org.uk.

MeSH Terms

  • Amino Acid Sequence
  • Animals
  • Antigenic Variation
  • Epitope Mapping
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Horse Diseases / epidemiology
  • Horse Diseases / virology
  • Horses
  • Influenza A virus / chemistry
  • Influenza A virus / classification
  • Influenza A virus / genetics
  • Influenza A virus / immunology
  • Models, Molecular
  • Molecular Sequence Data
  • Orthomyxoviridae Infections / epidemiology
  • Orthomyxoviridae Infections / veterinary
  • Orthomyxoviridae Infections / virology
  • Phylogeny
  • Sequence Alignment
  • United Kingdom / epidemiology

Citations

This article has been cited 13 times.
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