Infection of peripheral blood mononuclear cells with neuropathogenic equine herpesvirus type-1 strain Ab4 reveals intact interferon-α induction and induces suppression of anti-inflammatory interleukin-10 responses in comparison to other viral strains.
Abstract: The recent increase in incidence, morbidity, and mortality of neurological disease induced by equine herpesvirus type 1 (EHV-1) has suggested a change of virulence of the virus. The exact mechanisms by which EHV-1 induces neurologic disease are not known. Environmental, viral, and host risk factors might contribute to neurological manifestation. Here, we investigated innate interferon-α (IFN-α), interleukin-10 (IL-10) and IL-4 responses after infection of equine peripheral blood mononuclear cells (PBMC) with EHV-1 using an available cytokine multiplex assay. Three viral strains representing an older isolate (RacL11), a recent abortigenic (NY03) and a neuropathogenic isolate (Ab4) were compared to identify differences in cytokine induction that might explain the increased pathogenicity of Ab4. Cytokine concentrations were also compared between foals, mares after birth, pregnant and non-pregnant mares to investigate whether immune responses to EHV-1 infection are influenced by age or pregnancy status. PBMC from all groups secreted high concentrations of anti-viral IFN-α in response to EHV-1. A reduced response was observed in foals compared to non-pregnant mares. EHV-1 infection induced moderate IL-10 and overall low IL-4 secretion. Ab4 infection resulted in a significant reduction of IL-10 responses in adult horses. IL-10 and IL-4 responses were lower in foals than in most mare groups. These data suggested that EHV-1 induces robust IFN-α secretion without major differences between viral strains. However, anti-inflammatory IL-10 production was significantly reduced after infection with neuropathogenic Ab4. The ability of this EHV-1 isolate to down-regulate IL-10 production might contribute to increased local inflammation and a higher risk for neurological manifestation of the disease after infection with Ab4.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication Date: 2011-06-28 PubMed ID: 21764140DOI: 10.1016/j.vetimm.2011.06.032Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research paper investigates the effect of various strains of equine herpesvirus type 1 (EHV-1) on the immune response of horses, with particular focus on the neuropathogenic strain Ab4. It finds that while all EHV-1 strains prompt the production of anti-viral interferon-α (IFN-α), the Ab4 strain significantly reduces the anti-inflammatory response of interleukin-10 (IL-10), potentially leading to higher inflammation and increased risk of neurological symptoms.
Methodology
- Researchers infected equine peripheral blood mononuclear cells (PBMCs) with three strains of EHV-1: RacL11 (an older isolate), NY03 (a recent abortigenic strain), and Ab4 (a neuropathogenic isolate).
- They used a cytokine multiplex assay to measure the production of IFN-α, IL-10, and IL-4 (key components of the immune response) following infection with these strains.
- They compared the responses among foals, mares post-birth, and pregnant and non-pregnant mares to explore whether age or pregnancy status influenced immune responses to EHV-1.
Findings
- The researchers found that PBMCs secreted high concentrations of anti-viral IFN-α in response to all strains of EHV-1, with a lower response seen in foals compared to non-pregnant mares.
- They observed moderate IL-10 and somewhat low IL-4 secretion following EHV-1 infection, but the neuropathogenic Ab4 strain resulted in a significant reduction of IL-10 responses in adult horses.
- IL-10 and IL-4 responses were lower in foals than in most mare groups.
Implications
- The findings suggest that while EHV-1 prompts a strong IFN-α response regardless of the strain, the neuropathogenic Ab4 strain has the unique effect of reducing anti-inflammatory IL-10 production.
- This lowered IL-10 response could contribute to increased local inflammation and a higher risk for neurological symptoms following infection with Ab4 strain.
- This understanding could help in developing targeted therapies for EHV-1, particularly for affected horses presenting with neurological symptoms.
Cite This Article
APA
Wagner B, Wimer C, Freer H, Osterrieder N, Erb HN.
(2011).
Infection of peripheral blood mononuclear cells with neuropathogenic equine herpesvirus type-1 strain Ab4 reveals intact interferon-α induction and induces suppression of anti-inflammatory interleukin-10 responses in comparison to other viral strains.
Vet Immunol Immunopathol, 143(1-2), 116-124.
https://doi.org/10.1016/j.vetimm.2011.06.032 Publication
Researcher Affiliations
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. bw73@cornell.edu
MeSH Terms
- Animals
- Animals, Newborn
- Female
- Herpesviridae Infections / immunology
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Herpesvirus 1, Equid / classification
- Herpesvirus 1, Equid / immunology
- Herpesvirus 1, Equid / pathogenicity
- Horse Diseases / immunology
- Horse Diseases / virology
- Horses / immunology
- Horses / virology
- Immune Tolerance
- Interferon-alpha / biosynthesis
- Interleukin-10 / biosynthesis
- Interleukin-4 / biosynthesis
- Leukocytes, Mononuclear / immunology
- Leukocytes, Mononuclear / virology
- Pregnancy
- Pregnancy Complications, Infectious / immunology
- Pregnancy Complications, Infectious / veterinary
- Pregnancy Complications, Infectious / virology
- Species Specificity
Citations
This article has been cited 16 times.- Black JB, Frampton AR. Anti-inflammatory compounds reduce equine herpesvirus type 1 replication and cell-to-cell spread.. Front Vet Sci 2023;10:1165917.
- Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G. A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.. Front Vet Sci 2021;8:674850.
- Zarski LM, Weber PSD, Lee Y, Soboll Hussey G. Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection.. Pathogens 2021 Jan 7;10(1).
- Giessler KS, Samoilowa S, Soboll Hussey G, Kiupel M, Matiasek K, Sledge DG, Liesche F, Schlegel J, Fux R, Goehring LS. Viral Load and Cell Tropism During Early Latent Equid Herpesvirus 1 Infection Differ Over Time in Lymphoid and Neural Tissue Samples From Experimentally Infected Horses.. Front Vet Sci 2020;7:621.
- Pavulraj S, Kamel M, Stephanowitz H, Liu F, Plendl J, Osterrieder N, Azab W. Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs.. Viruses 2020 Sep 8;12(9).
- Oladunni FS, Sarkar S, Reedy S, Balasuriya UBR, Horohov DW, Chambers TM. Equid Herpesvirus 1 Targets the Sensitization and Induction Steps To Inhibit the Type I Interferon Response in Equine Endothelial Cells.. J Virol 2019 Dec 1;93(23).
- Kim SK, Shakya AK, O'Callaghan DJ. Intranasal treatment with CpG-B oligodeoxynucleotides protects CBA mice from lethal equine herpesvirus 1 challenge by an innate immune response.. Antiviral Res 2019 Sep;169:104546.
- Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H, Stout AE, Rollins A, Osterrieder N, Goodman LB, Glaser A, Wagner B. The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses.. PLoS One 2018;13(11):e0206679.
- Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Soboll Hussey G, Maes RK, Nauwynck HJ. Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense.. Front Cell Infect Microbiol 2018;8:312.
- Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H, Watts C, Rollins A, Osterrieder N, Wagner B. Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity.. BMC Vet Res 2018 Aug 22;14(1):245.
- Hue ES, Richard EA, Fortier CI, Fortier GD, Paillot R, Raue R, Pronost SL. Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment.. Vaccines (Basel) 2017 Sep 19;5(3).
- Stasiak K, Dunowska M, Hills SF, Rola J. Genetic characterization of equid herpesvirus type 1 from cases of abortion in Poland.. Arch Virol 2017 Aug;162(8):2329-2335.
- Wagner B, Perkins G, Babasyan S, Freer H, Keggan A, Goodman LB, Glaser A, Torsteinsdóttir S, Svansson V, Björnsdóttir S. Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1) at Weanling Age.. PLoS One 2017;12(1):e0169072.
- Negussie H, Li Y, Tessema TS, Nauwynck HJ. Replication characteristics of equine herpesvirus 1 and equine herpesvirus 3: comparative analysis using ex vivo tissue cultures.. Vet Res 2016 Jan 15;47:19.
- Detournay O, Morrison DA, Wagner B, Zarnegar B, Wattrang E. Genomic analysis and mRNA expression of equine type I interferon genes.. J Interferon Cytokine Res 2013 Dec;33(12):746-59.
- Goodman LB, Wimer C, Dubovi EJ, Gold C, Wagner B. Immunological correlates of vaccination and infection for equine herpesvirus 1.. Clin Vaccine Immunol 2012 Feb;19(2):235-41.
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