Analyze Diet
Transboundary and emerging diseases2021; 69(4); e52-e63; doi: 10.1111/tbed.14262

Genome-informed characterisation of antigenic drift in the haemagglutinin gene of equine influenza strains circulating in the United States from 2012 to 2017.

Abstract: Equine influenza virus (EIV) is a major infectious pathogen causing significant respiratory signs in equids worldwide. Voluntary surveillances in the United States recently reported EIV detection in horses with respiratory signs even with adequate vaccine protocols and biosecurity programs and posed a concern about suboptimal effectiveness of EIV vaccine in the United States. This study aims to determine the genetic characteristics of 58 field EIV H3N8 strains in the United States from 2012 to 2017 using the phylogenetic analysis based on the haemagglutinin (HA) gene. Amino acid substitution and acquisition of N-glycosylation of the HA gene were also evaluated. Phylogenetic analysis identified that almost all US field strains belonged to the Florida clade 1 (FC1) except one Florida clade 2 strain from a horse imported in 2014. US EIV strains in 2017 shared 11 fixed amino acid substitutions in the HA gene, compared to the vaccine strain (A/equine/Ohio/2003), and two additional amino acid substitutions were detected in 2019. The introduction of foreign EIV strains into the United States was not detected, but antigenic drift without acquisition of N-glycosylation in the HA gene was observed in US field strains until 2017. Considering the global dominance of FC1 strains, subsequent antigenic drift of US EIV strains should be monitored for better effectiveness of the EIV vaccine in the United States and global equine industries.
Publication Date: 2021-08-17 PubMed ID: 34331828DOI: 10.1111/tbed.14262Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

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 paper conducts a genetic study of equine influenza virus (EIV) strains in the US from 2012 to 2017 to understand the variations that may be causing the virus to persist in vaccinated horses.

Objective of the Study

  • The aim of this study is to determine the genetic features of 58 types of EIV H3N8 strains that were predominant in the United States between 2012 and 2017. The study focuses specifically on the haemagglutinin (HA) gene, which influences the virus’s ability to infect host cells.
  • Recent voluntary surveillances have shown the presence of EIV in horses showing respiratory symptoms despite adequate vaccination and biosecurity protocols. This raises concerns over the effectiveness of the current EIV vaccine in the US.

Methodology and Findings

  • The researchers used phylogenetic analysis, a method of reconstructing the evolutionary relationships between different strains of a virus based on their genetic characteristics. They found that almost all of the 58 EIV strains belonged to the Florida Clade 1 (FC1) family of the virus.
  • When comparing the US EIV strains from 2017 with the vaccine strain (A/equine/Ohio/2003), 11 fixed amino acid substitutions were observed in the HA gene. An additional two amino acid substitutions were detected in 2019.
  • No evidence of foreign EIV strains being introduced into the US was found. However, antigenic drift, a process by which the virus evolves and changes over time, was observed. Importantly, such drift was happening without the acquisition of N-glycosylation, a process that adds a sugar molecule to a protein – critical for its structure and function – in the HA gene.

Implications of the Findings

  • Given the global dominance of FC1 strains and the observed antigenic drift in the US EIV strains, the study emphasizes the need for careful ongoing monitoring.
  • This surveillance will enable the adaptation of EIV vaccination strategies, enhancing their effectiveness not only in the US but also in equine industries globally.
  • The lack of N-glycosylation in the HA gene despite antigenic drift poses interesting questions for further research regarding how the EIV virus is evolving within the US horse population.

Cite This Article

APA
Lee K, Pusterla N, Barnum SM, Lee DH, Martínez-López B. (2021). Genome-informed characterisation of antigenic drift in the haemagglutinin gene of equine influenza strains circulating in the United States from 2012 to 2017. Transbound Emerg Dis, 69(4), e52-e63. https://doi.org/10.1111/tbed.14262

Publication

ISSN: 1865-1682
NlmUniqueID: 101319538
Country: Germany
Language: English
Volume: 69
Issue: 4
Pages: e52-e63

Researcher Affiliations

Lee, Kyuyoung
  • Center for Animal Disease Modeling and Surveillance (CADMS), Department of Medicine & Epidemiology, School of Veterinary Medicine, University of California, Davis, USA.
Pusterla, Nicola
  • Department of Medicine & Epidemiology, School Veterinary Medicine, University of California, Davis, USA.
Barnum, Samantha M
  • Department of Medicine & Epidemiology, School Veterinary Medicine, University of California, Davis, USA.
Lee, Dong-Hun
  • Department of Pathobiology and Veterinary Science, the University of Connecticut, Storrs, Connecticut, USA.
Martínez-López, Beatriz
  • Center for Animal Disease Modeling and Surveillance (CADMS), Department of Medicine & Epidemiology, School of Veterinary Medicine, University of California, Davis, USA.

MeSH Terms

  • Animals
  • Antigenic Drift and Shift
  • Hemagglutinins / genetics
  • Horse Diseases / diagnosis
  • Horses
  • Humans
  • Influenza A Virus, H3N8 Subtype / genetics
  • Influenza, Human
  • Orthomyxoviridae Infections / diagnosis
  • Orthomyxoviridae Infections / epidemiology
  • Orthomyxoviridae Infections / veterinary
  • Phylogeny

Grant Funding

  • Center for Equine Health (CEH) grant award at UC Davis
  • Graduate group in epidemiology Fellowship at UC Davis
  • Graduate Student Support Program (GSSP) in the School of Veterinary Medicine at UC Davis
  • #1838207 / US National Science Foundation (NSF)

References

This article includes 61 references
  1. Baele G, Lemey P, Bedford T, Rambaut A, Suchard MA, Alekseyenko AV. Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty. Molecular Biology and Evolution 29, 2157-2167.
    doi: 10.1093/molbev/mss084google scholar: lookup
  2. Binns MM, Daly JM, Chirnside ED, Mumford JA, Wood JM, Richards CM, Daniels RS. Genetic and antigenic analysis of an equine influenza H 3 isolate from the 1989 epidemic. Archives of Virology 130, 33-43.
  3. Bryant NA, Rash AS, Russell CA, Ross J, Cooke A, Bowman S, MacRae S, Lewis NS, Paillot R, Zanoni R. Antigenic and genetic variations in European and North American equine influenza virus strains (H3N8) isolated from 2006 to 2007. Veterinary Microbiology 138, 41-52.
  4. Chang D, Zaia J. Why glycosylation matters in building a better flu vaccine. Molecular & Cellular Proteomics 18, 2348-2358.
    doi: 10.1074/mcp.r119.001491google scholar: lookup
  5. Chatham House (2018). Resourcetrade. earth. Chatham House. https://resourcetrade.earth/data
  6. Compans RW, Oldstone MB. Influenza pathogenesis and control (Vol. 1). .
  7. Cowled B, Ward MP, Hamilton S, Garner G. The equine influenza epidemic in Australia: spatial and temporal descriptive analyses of a large propagating epidemic. Preventive Veterinary Medicine 92, 60-70.
  8. Crawford PC, Dubovi EJ, Castleman WL, Stephenson I, Gibbs EPJ, Chen L, Smith C, Hill RC, Ferro P, Pompey J. Transmission of equine influenza virus to dogs. Science 310, 482-485.
  9. Criado MF, Bertran K, Lee D-H, Killmaster L, Stephens CB, Spackman E, Sa e Silva M, Atkins E, Mebatsion T, Widener J, Pritchard N, King H, Swayne DE. Efficacy of novel recombinant fowlpox vaccine against recent Mexican H7N3 highly pathogenic avian influenza virus. Vaccine 37, 2232-2243.
  10. Cullinane A, Newton JR. Equine influenza-a global perspective. Veterinary Microbiology 167, 205-214.
  11. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Research 32, 1792-1797.
  12. Gao J, Couzens L, Burke DF, Wan H, Wilson P, Memoli MJ, Xu X, Harvey R, Wrammert J, Ahmed R. Antigenic drift of the influenza A (H1N1) pdm09 virus neuraminidase results in reduced effectiveness of A/California/7/2009 (H1N1pdm09)-specific antibodies. mBio 10(2), e00307.
  13. Gardy JL, Loman NJ. Towards a genomics-informed, real-time, global pathogen surveillance system. Nature Reviews Genetics 19, 9-20.
  14. Gildea S, Quinlivan M, Arkins S, Cullinane A. The molecular epidemiology of equine influenza in Ireland from 2007-2010 and its international significance. Equine Veterinary Journal 44, 387-392.
  15. Grenfell BT, Pybus OG, Gog JR, Wood JL, Daly JM, Mumford JA, Holmes EC. Unifying the epidemiological and evolutionary dynamics of pathogens. Science 303, 327-332.
  16. Gupta R, Brunak S. Prediction of glycosylation across the human proteome and the correlation to protein function. Pacific Symposium on Biocomputing 7, 310-322.
  17. Hasegawa M, Kishino H, Yano T. Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. Journal of Molecular Evolution 22, 160-174.
  18. Hicks JT, Lee D-H, Duvvuri VR, Torchetti MK, Swayne DE, Bahl J. Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak. PLoS Pathogens 16, e1007857.
  19. Ito M, Nagai M, Hayakawa Y, Komae H, Murakami N, Yotsuya S, Asakura S, Sakoda Y, Kida H. Genetic analyses of an H3N8 influenza virus isolate, causative strain of the outbreak of equine influenza at the Kanazawa racecourse in Japan in 2007. Journal of Veterinary Medical Science 70, 899-906.
  20. Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nature Methods 14, 587-589.
    doi: 10.1038/nmeth.4285google scholar: lookup
  21. Katoh K, Misawa K, Kuma K, Miyata T. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Research 30, 3059-3066.
  22. Koel BF, Burke DF, Bestebroer TM, van der Vliet S, Zondag GCM, Vervaet G, Skepner E, Lewis NS, Spronken MIJ, Russell CA, Eropkin MY, Hurt AC, Barr IG, de Jong JC, Rimmelzwaan GF, Osterhaus ADME, Fouchier RAM, Smith DJ. Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. Science 342, 976-979.
    doi: 10.1126/science.1244730google scholar: lookup
  23. Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Molecular Biology and Evolution 33, 1870-1874.
  24. Lai AC, Lin YP, Powell DG, Shortridge KF, Webster RG, Daly J, Chambers TM. Genetic and antigenic analysis of the influenza virus responsible for the 1992 Hong Kong equine influenza epizootic. Virology 204, 673-679.
  25. Legrand L, Pitel P, Cullinane A, Fortier G, Pronost S. Genetic evolution of equine influenza strains isolated in France from 2005 to 2010. Equine Veterinary Journal 47, 207-211.
  26. Lewis NS, Anderson TK, Kitikoon P, Skepner E, Burke DF, Vincent AL. Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine. Journal of Virology 88, 4752-4763.
    doi: 10.1128/jvi.03805-13google scholar: lookup
  27. Lewis NS, Daly JM, Russell CA, Horton DL, Skepner E, Bryant NA, Burke DF, Rash AS, Wood JLN, Chambers TM. Antigenic and genetic evolution of equine influenza A (H3N8) virus from 1968 to 2007. Journal of Virology 85, 12742-12749.
  28. Livesay GJ, O'neill T, Hannant D, Yadav MP, Mumford JA. The outbreak of equine influenza (H3N8) in the United Kingdom in 1989: diagnostic use of an antigen capture ELISA. The Veterinary Record 133, 515-519.
  29. Miller MA, Pfeiffer W, Schwartz T. The CIPRES science gateway: a community resource for phylogenetic analyses. Proceedings of the 2011 TeraGrid Conference: Extreme Digital Discovery, New York, NY, United States (pp. 1-8) .
  30. Miño S, Mojsiejczuk L, Guo W, Zhang H, Qi T, Du C, Zhang X, Wang J, Campos R, Wang X. Equine influenza virus in Asia: phylogeographic pattern and molecular features reveal circulation of an autochthonous lineage. Journal of Virology 93(13), e00116-19.
  31. Murcia PR, Wood JL, Holmes EC. Genome-scale evolution and phylodynamics of equine H3N8 influenza A virus. Journal of Virology 85, 5312-5322.
  32. Nemoto M, Yamayoshi S, Bannai H, Tsujimura K, Kokado H, Kawaoka Y, Yamanaka T. A single amino acid change in hemagglutinin reduces the cross-reactivity of antiserum against an equine influenza vaccine strain. Archives of Virology 164, 2355-2358.
  33. Newton JR, Daly JM, Spencer L, Mumford JA. Description of the outbreak of equine influenza (H3N8) in the United Kingdom in 2003, during which recently vaccinated horses in Newmarket developed respiratory disease. Veterinary Record 158, 185-192.
  34. . Expert surveillance panel on equine influenza vaccine composition-conclusions and recommendations. Office International des Epizooties Bulletin .
  35. . Expert surveillance panel on equine influenza vaccine composition-conclusions and recommendations. Office International des Epizooties Bulletin .
  36. . Expert surveillance panel on equine influenza vaccine composition-conclusions and recommendations. Office International des Epizooties Bulletin .
  37. Powell H, Pekosz A. Neuraminidase antigenic drift of H3N2 clade 3c. 2a viruses alters virus replication, enzymatic activity and inhibitory antibody binding. PLoS Pathogens 16, e1008411.
  38. Pusterla N, Estell K, Mapes S, Wademan C. Detection of clade 2 equine influenza virus in an adult horse recently imported to the USA. Equine Veterinary Education 26, 453-455.
  39. Pusterla N, Kass PH, Mapes S, Johnson C, Barnett DC, Vaala W, Gutierrez C, McDaniel R, Whitehead B, Manning J. Surveillance programme for important equine infectious respiratory pathogens in the USA. Veterinary Record 169(1), 12.
  40. Pusterla N, Kass PH, Mapes S, Wademan C, Akana N, Barnett C, MacKenzie C, Vaala W. Voluntary surveillance program for equine influenza virus in the United States from 2010 to 2013. Journal of Veterinary Internal Medicine 29, 417-422.
  41. Rambaut A, Drummond A. TreeAnnotator v1.10.5. (Part of the BEAST package). .
  42. Rambaut A, Drummond AJ, Xie D, Baele G, Suchard MA. Posterior summarization in Bayesian phylogenetics using Tracer 1.7. Systematic Biology 67, 901-904.
  43. Rambaut A, Lam TT, Carvalho LM, Pybus OG. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Virus Evolution 2, vew007.
    doi: 10.1093/ve/vew007google scholar: lookup
  44. Rodriguez L, Reedy S, Nogales A, Murcia PR, Chambers TM, Martinez-Sobrido L. Development of a novel equine influenza virus live-attenuated vaccine. Virology 516, 76-85.
  45. Rosanowski SM, Carpenter TE, Adamson D, Rogers CW, Pearce P, Burns M, Cogger N. An economic analysis of a contingency model utilising vaccination for the control of equine influenza in a non-endemic country. PLoS One 14, e0210885.
  46. Russell CJ, Hu M, Okda FA. Influenza hemagglutinin protein stability, activation, and pandemic risk. Trends in Microbiology 26(10), 841-853.
  47. Scholtens RG, Steele JH, Dowdle WR, Yarbrough WB, Robinson RQ. US epizootic of equine influenza, 1963. Public Health Reports (Washington, DC: 1896) 79, 393-402.
  48. Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. Mapping the antigenic and genetic evolution of influenza virus. Science 305, 371-376.
  49. Smyth GB, Dagley K, Tainsh J. Insights into the economic consequences of the 2007 equine influenza outbreak in Australia. Australian Veterinary Journal 89, 151-158.
  50. Sovinova O, Tumova B, Pouska F, Nemec J. Isolation of a virus causing respiratory disease in horses. Acta Virologica 2, 52.
  51. Sreenivasan C, Jandhyala S, Luo S, Hause B, Thomas M, Knudsen D, Leslie-Steen P, Clement T, Reedy S, Chambers T. Phylogenetic analysis and characterization of a sporadic isolate of equine influenza A H3N8 from an unvaccinated horse in 2015. Viruses 10, 31.
  52. Suchard MA, Lemey P, Baele G, Ayres DL, Drummond AJ, Rambaut A. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evolution 4, vey016.
    doi: 10.1093/ve/vey016google scholar: lookup
  53. Suchard MA, Weiss RE, Sinsheimer JS. Bayesian selection of continuous-time Markov Chain Evolutionary Models. Molecular Biology and Evolution 18(6), 1001-1013.
  54. Webster RG. Are equine 1 influenza viruses still present in horses?. Equine Veterinary Journal 25, 537-538.
  55. Wiley D, Wilson I, Skehel J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289, 373-378.
  56. Wilson IA, Cox NJ. Structural basis of immune recognition of influenza virus hemagglutinin. Annual Review of Immunology 8, 737-787.
  57. Woodward A, Rash AS, Medcalf E, Bryant NA, Elton DM. Using epidemics to map H3 equine influenza virus determinants of antigenicity. Virology 481, 187-198.
  58. Woodward AL, Rash AS, Blinman D, Bowman S, Chambers TM, Daly JM, Damiani A, Joseph S, Lewis N, McCauley JW, Medcalf L, Mumford J, Newton JR, Tiwari A, Bryant NA, Elton DM. Development of a surveillance scheme for equine influenza in the UK and characterisation of viruses isolated in Europe, Dubai and the USA from 2010-2012. Veterinary Microbiology 169, 113-127.
  59. Xie W, Lewis PO, Fan Y, Kuo L, Chen M-H. Improving marginal likelihood estimation for Bayesian phylogenetic model selection. Systematic Biology 60, 150-160.
  60. Yamanaka T, Niwa H, Tsujimura K, Kondo T, Matsumura T. Epidemic of equine influenza among vaccinated racehorses in Japan in 2007. Journal of Veterinary Medical Science 70, 623-625.
  61. Ye J, Xu Y, Harris J, Sun H, Bowman AS, Cunningham F, Cardona C, Yoon KJ, Slemons RD, Wan X-F. Mutation from arginine to lysine at the position 189 of hemagglutinin contributes to the antigenic drift in H3N2 swine influenza viruses. Virology 446, 225-229.

Citations

This article has been cited 5 times.
  1. Wasik BR, Rothschild E, Voorhees IEH, Reedy SE, Murcia PR, Pusterla N, Chambers TM, Goodman LB, Holmes EC, Kile JC, Parrish CR. Understanding the divergent evolution and epidemiology of H3N8 influenza viruses in dogs and horses. Virus Evol 2023;9(2):vead052.
    doi: 10.1093/ve/vead052pubmed: 37692894google scholar: lookup
  2. Chappell DE, Barnett DC, James K, Craig B, Bain F, Gaughan E, Schneider C, Vaala W, Barnum SM, Pusterla N. Voluntary Surveillance Program for Equine Influenza Virus in the United States during 2008-2021. Pathogens 2023 Jan 27;12(2).
    doi: 10.3390/pathogens12020192pubmed: 36839464google scholar: lookup
  3. Gonzalez-Obando J, Forero JE, Zuluaga-Cabrera AM, Ruiz-Saenz J. Equine Influenza Virus: An Old Known Enemy in the Americas. Vaccines (Basel) 2022 Oct 14;10(10).
    doi: 10.3390/vaccines10101718pubmed: 36298583google scholar: lookup
  4. Gonzalez-Obando J, Jaimes-Dueñez J, Zuluaga-Cabrera A, Forero JE, Diaz A, Rojas-Arbeláez C, Ruiz-Saenz J. Seroprevalence of Equine Influenza Virus Antibodies in Horses from Four Localities in Colombia. Viruses 2025 Jul 16;17(7).
    doi: 10.3390/v17070999pubmed: 40733615google scholar: lookup
  5. Kleij L, Bruder E, Raoux-Barbot D, Lejal N, Nevers Q, Deloizy C, Da Costa B, Legrand L, Barrey E, Chenal A, Pronost S, Delmas B, Dhorne-Pollet S. Genomic characterization of equine influenza A subtype H3N8 viruses by long read sequencing and functional analyses of the PB1-F2 virulence factor of A/equine/Paris/1/2018. Vet Res 2024 Mar 22;55(1):36.
    doi: 10.1186/s13567-024-01289-8pubmed: 38520035google scholar: lookup