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Veterinary research2024; 55(1); 36; doi: 10.1186/s13567-024-01289-8

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.

Abstract: Equine influenza virus (EIV) remains a threat to horses, despite the availability of vaccines. Strategies to monitor the virus and prevent potential vaccine failure revolve around serological assays, RT-qPCR amplification, and sequencing the viral hemagglutinin (HA) and neuraminidase (NA) genes. These approaches overlook the contribution of other viral proteins in driving virulence. This study assesses the potential of long-read nanopore sequencing for fast and precise sequencing of circulating equine influenza viruses. Therefore, two French Florida Clade 1 strains, including the one circulating in winter 2018-2019 exhibiting more pronounced pathogenicity than usual, as well as the two currently OIE-recommended vaccine strains, were sequenced. Our results demonstrated the reliability of this sequencing method in generating accurate sequences. Sequence analysis of HA revealed a subtle antigenic drift in the French EIV strains, with specific substitutions, such as T163I in A/equine/Paris/1/2018 and the N188T mutation in post-2015 strains; both substitutions were in antigenic site B. Antigenic site E exhibited modifications in post-2018 strains, with the N63D substitution. Segment 2 sequencing also revealed that the A/equine/Paris/1/2018 strain encodes a longer variant of the PB1-F2 protein when compared to other Florida clade 1 strains (90 amino acids long versus 81 amino acids long). Further biological and biochemistry assays demonstrated that this PB1-F2 variant has enhanced abilities to abolish the mitochondrial membrane potential ΔΨm and permeabilize synthetic membranes. Altogether, our results highlight the interest in rapidly characterizing the complete genome of circulating strains with next-generation sequencing technologies to adapt vaccines and identify specific virulence markers of EIV.
© 2024. The Author(s).
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Publication Date: 2024-03-22 PubMed ID: 38520035PubMed Central: PMC10960481DOI: 10.1186/s13567-024-01289-8Google Scholar: Lookup
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  • 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.

Overview

  • This study used long-read nanopore sequencing to analyze the complete genomes of equine influenza A/H3N8 viruses, focusing on strains circulating in France, including one with increased pathogenicity in 2018-2019.
  • The research identified mutations in viral proteins, particularly a longer PB1-F2 protein variant, that may contribute to virulence and vaccine adaptation strategies.

Background and Objectives

  • Equine influenza virus (EIV) is a contagious respiratory disease in horses, posing ongoing challenges despite vaccine availability.
  • Current monitoring of EIV primarily targets the hemagglutinin (HA) and neuraminidase (NA) genes via serology, RT-qPCR, and partial sequencing.
  • These methods may fail to detect changes in other viral proteins that influence virulence.
  • The primary objective was to evaluate the use of long-read nanopore sequencing for comprehensive, rapid genomic characterization of EIV strains.
  • Additionally, the study aimed to functionally analyze the PB1-F2 protein variant found in a notably pathogenic 2018 French EIV strain.

Methodology

  • Selected viral strains included two Florida Clade 1 strains from France, including the 2018-2019 highly pathogenic A/equine/Paris/1/2018, and two OIE-recommended vaccine strains.
  • Long-read nanopore sequencing technology was applied to generate full-length genome sequences rapidly and with high accuracy.
  • Comparative sequence analyses focused on mutations within antigenic sites of HA and variations in segment 2, which encodes PB1-F2.
  • Functional assays were conducted to assess the biological effects of the PB1-F2 protein variants, including impacts on mitochondrial membrane potential and membrane permeabilization.

Key Findings

  • Nanopore sequencing reliably delivered accurate, complete genomic sequences of EIV strains in a fast and efficient manner.
  • HA gene analysis revealed subtle antigenic drift:
    • T163I substitution in the A/equine/Paris/1/2018 strain and N188T mutation in strains post-2015, both located in antigenic site B.
    • Post-2018 strains showed mutations in antigenic site E, including N63D substitution.
  • Segment 2 sequencing identified a longer PB1-F2 protein variant in the 2018-2019 Paris strain, extending to 90 amino acids versus the typical 81 amino acids seen in other Florida Clade 1 strains.
  • Functional and biochemical assays demonstrated that this longer PB1-F2 variant more effectively disrupted mitochondrial membrane potential (ΔΨm) and permeabilized synthetic membranes, suggesting enhanced virulence mechanisms.

Implications and Conclusions

  • The study highlights the benefit of using next-generation, long-read sequencing to rapidly obtain complete EIV genomic data beyond HA and NA genes.
  • Understanding changes in proteins like PB1-F2, which can affect virulence, is critical for monitoring virus evolution and for adapting vaccines to emerging strains.
  • Detection of antigenic drift in key HA sites indicates the potential for vaccine mismatch and underscores the need for continual genomic surveillance.
  • The discovery of a longer and functionally more active PB1-F2 variant in a highly pathogenic strain suggests that this protein could be a virulence marker worth monitoring in future outbreaks.
  • Overall, comprehensive genome sequencing coupled with functional protein analysis can enhance equine influenza virus surveillance, improve vaccine design, and help prevent disease outbreaks in horse populations.

Cite This Article

APA
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. (2024). 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, 55(1), 36. https://doi.org/10.1186/s13567-024-01289-8

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 55
Issue: 1
Pages: 36
PII: 36

Researcher Affiliations

Kleij, Lena
  • Unité de Virologie et Immunologie Moléculaires, INRAE, UVSQ, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Bruder, Elise
  • Unité de Virologie et Immunologie Moléculaires, INRAE, UVSQ, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Raoux-Barbot, Dorothée
  • CNRS UMR 3528, Biochemistry of Macromolecular Interactions Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, 75015, Paris, France.
Lejal, Nathalie
  • Unité de Virologie et Immunologie Moléculaires, INRAE, UVSQ, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Nevers, Quentin
  • Unité de Virologie et Immunologie Moléculaires, INRAE, UVSQ, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Deloizy, Charlotte
  • Unité de Virologie et Immunologie Moléculaires, INRAE, UVSQ, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Da Costa, Bruno
  • Unité de Virologie et Immunologie Moléculaires, INRAE, UVSQ, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Legrand, Loïc
  • LABÉO Frank Duncombe, 14280, Saint-Contest, France.
  • BIOTARGEN, Normandie Univ, UNICAEN, 14000, Caen, France.
Barrey, Eric
  • AgroParisTech, Unité de Génétique Animale et Biologie Intégrative, INRAE, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Chenal, Alexandre
  • CNRS UMR 3528, Biochemistry of Macromolecular Interactions Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, 75015, Paris, France.
Pronost, Stéphane
  • LABÉO Frank Duncombe, 14280, Saint-Contest, France.
  • BIOTARGEN, Normandie Univ, UNICAEN, 14000, Caen, France.
Delmas, Bernard
  • Unité de Virologie et Immunologie Moléculaires, INRAE, UVSQ, Université Paris-Saclay, 78350, Jouy-en-Josas, France. bernard.delmas@inrae.fr.
Dhorne-Pollet, Sophie
  • AgroParisTech, Unité de Génétique Animale et Biologie Intégrative, INRAE, Université Paris-Saclay, 78350, Jouy-en-Josas, France.

MeSH Terms

  • Animals
  • Amino Acids / genetics
  • Genomics
  • Horse Diseases
  • Horses
  • Influenza A Virus, H3N8 Subtype / genetics
  • Orthomyxoviridae Infections / veterinary
  • Reproducibility of Results
  • Sequence Analysis / veterinary
  • Vaccines
  • Virulence Factors

Grant Funding

  • CS-2020-2023-029-EquInfluenza / IFCE
  • N23-2020 / Fonds Eperon

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 1 times.
  1. Branda F, Yon DK, Albanese M, Binetti E, Giovanetti M, Ciccozzi A, Ciccozzi M, Scarpa F, Ceccarelli G. Equine Influenza: Epidemiology, Pathogenesis, and Strategies for Prevention and Control. Viruses 2025 Feb 21;17(3).
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