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The Journal of general virology2024; 105(5); doi: 10.1099/jgv.0.001987

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses.

Abstract: Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1β, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-β (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this 'at-risk' immunophenotype.
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Publication Date: 2024-05-20 PubMed ID: 38767608PubMed Central: PMC11170125DOI: 10.1099/jgv.0.001987Google Scholar: Lookup
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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 study examines the role of the host’s immune response on the development of equine herpesvirus myeloencephalopathy (EHM), a potentially fatal disease in horses. The findings suggest that protective immunity against EHM depends on a timely immune response, and changes in immunity types may increase chances of developing the disease, indicating a possible direction for future vaccine development.

Study Design and Overview

  • This study uses older female horses as a model to identify host-specific factors contributing to EHM. The female horses and yearling horses were infected with a neuropathogenic strain of equine herpesvirus 1 (EHV-1).
  • Post-infection, the animals’ health and immune responses were tracked for 21 days. Measurements were taken of nasal viral shedding, cell-associated viremia, and immune responses in nasal secretions, cerebrospinal fluid, and blood.
  • In light of the animals’ clinical manifestations, the horses were split into two groups (EHM and non-EHM) for further analysis of their immune responses.

Results and Findings

  • All young horses developed respiratory illness but only 1 out of 9 showed signs of EHM. Older mares did not exhibit respiratory problems, but all developed EHM, which led to euthanasia in 6 out of 9 cases.
  • The non-EHM horses showed an early upregulation of certain immune markers in nasal secretions and blood. On the other hand, EHM horses showed low levels of IFN-α in nasal secretions and peak levels of a range of immune markers coinciding with viremia. Furthermore, EHM horses displayed superior IL-10 levels in nasal secretions, peripheral blood mononuclear cells, and CSF.
  • Results seem to suggest that the timely induction of certain types of immunity (type 1 IFN and cellular immunity) may provide protection from EHM. However, the induction of regulatory or TH-2 type immunity may correlate with an increased risk for developing EHM.

Implications and Future Research

  • The findings from this study indicate that future vaccine development for protection from EHM should aim at shifting the ‘at-risk’ immunophenotype.
  • Understanding the role of the host’s immune response in disease progression remains crucial. More research is needed to further uncover the specific elements and mechanisms involved.

Cite This Article

APA
Giessler KS, Goehring LS, Jacob SI, Davis A, Esser MM, Lee Y, Zarski LM, Weber PSD, Hussey GS. (2024). Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses. J Gen Virol, 105(5). https://doi.org/10.1099/jgv.0.001987

Publication

The Journal of general virology
ISSN: 1465-2099
NlmUniqueID: 0077340
Country: England
Language: English
Volume: 105
Issue: 5

Researcher Affiliations

Giessler, K S
  • Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
  • Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.
Goehring, L S
  • MH Gluck Equine Research Center, College of Agriculture, Food & Environment, University of Kentucky, Lexington, KY, USA.
Jacob, S I
  • Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Davis, Allison
  • Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Esser, M M
  • Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Lee, Y
  • Pathology Core, Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA.
Zarski, L M
  • Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Weber, P S D
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Hussey, G S
  • Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.

MeSH Terms

  • Animals
  • Horses
  • Herpesvirus 1, Equid / immunology
  • Female
  • Horse Diseases / virology
  • Horse Diseases / immunology
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / virology
  • Cytokines / blood
  • Cytokines / immunology
  • Antibodies, Viral / blood
  • Virus Shedding
  • Viremia / immunology
  • Viremia / veterinary
  • Immunoglobulin G / blood

Conflict of Interest Statement

The authors declare that there are no conflicts of interest.

References

This article includes 124 references
  1. Davison AJ. Evolution of the herpesviruses.. Vet Microbiol 2002;86:69–88.
    doi: 10.1016/s0378-1135(01)00492-8pubmed: 11888691google scholar: lookup
  2. Orthoherpesviridae: ICTV International Committee on Taxonomy of Viruses. 2022. https://ictv.global/taxonomy/taxondetails?taxnode_id=202201411&taxon_name=Orthoherpesviridae
  3. Davison AJ, Eberle R, Ehlers B, Hayward GS, McGeoch DJ. The order Herpesvirales.. Arch Virol 2009;154:171–177.
    doi: 10.1007/s00705-008-0278-4pmc: PMC3552636pubmed: 19066710google scholar: lookup
  4. Gilkerson JR, Whalley JM, Drummer HE, Studdert MJ, Love DN. Epidemiology of EHV-1 and EHV-4 in the mare and foal populations on a Hunter Valley stud farm: are mares the source of EHV-1 for unweaned foals.. Vet Microbiol 1999;68:27–34.
    doi: 10.1016/s0378-1135(99)00058-9pubmed: 10501159google scholar: lookup
  5. Patel JR, Heldens J. Equine herpesviruses 1 (EHV-1) and 4 (EHV-4)--epidemiology, disease and immunoprophylaxis: a brief review.. Vet J 2005;170:14–23.
    doi: 10.1016/j.tvjl.2004.04.018pubmed: 15993786google scholar: lookup
  6. Pusterla N, Hussey GS, Goehring LS. Equine herpesvirus-1 myeloencephalopathy.. Vet Clin North Am Equine Pract 2022;38:339–362.
    doi: 10.1016/j.cveq.2022.05.006pubmed: 35811201google scholar: lookup
  7. Lesté-Lasserre C. Deadly viral outbreak ravages European horses.. Science 2021;371:1297.
    doi: 10.1126/science.371.6536.1297pubmed: 33766865google scholar: lookup
  8. Fédération Équestre Internationale EHV-1 Report: FEI. 2022. https://inside.fei.org/fei/your-role/veterinarians/biosecurity-movements/biosecurity/ehv-1/report
  9. Sutton G, Thieulent C, Fortier C, Hue ES, Marcillaud-Pitel C. Identification of a new equid herpesvirus 1 DNA polymerase (ORF30) genotype with the isolation of a C2254/H752 strain in French horses showing no major impact on the strain behaviour.. Viruses 2020;12:1160.
    doi: 10.3390/v12101160pmc: PMC7650556pubmed: 33066315google scholar: lookup
  10. Traub-Dargatz JL, Pelzel-McCluskey AM, Creekmore LH, Geiser-Novotny S, Kasari TR. Case-control study of a multistate equine herpesvirus myeloencephalopathy outbreak.. J Vet Intern Med 2013;27:339–346.
    doi: 10.1111/jvim.12051pubmed: 23398291google scholar: lookup
  11. Henninger RW, Reed SM, Saville WJ, Allen GP, Hass GF. Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center.. J Vet Intern Med 2007;21:157–165.
    doi: 10.1892/0891-6640(2007)21[157:oondcb]2.0.co;2pubmed: 17338164google scholar: lookup
  12. United States Department of Agriculture Equine Herpesvirus (EHV-1) - FINAL Situation Report: USDA. 2011. https://www.aphis.usda.gov/vs/nahss/equine/ehv/ehv_2011_final_sitrep_062311.pdf
  13. Pusterla N, Hussey GS. Equine herpesvirus 1 myeloencephalopathy. Veterinary Clinics of North America: Equine Practice 2014;30:489–506.
    doi: 10.1016/j.cveq.2014.08.006pubmed: 25300635google scholar: lookup
  14. Lunn DP, Davis-Poynter N, Flaminio MJ, Horohov DW, Osterrieder K. Equine herpesvirus-1 consensus statement.. J Vet Intern Med 2009;23:450–461.
    doi: 10.1111/j.1939-1676.2009.0304.xpubmed: 19645832google scholar: lookup
  15. Edington N, Smyth B, Griffiths L. The role of endothelial cell infection in the endometrium, placenta and foetus of equid herpesvirus 1 (EHV-1) abortions.. J Comp Pathol 1991;104:379–387.
    doi: 10.1016/s0021-9975(08)80148-xpubmed: 1651960google scholar: lookup
  16. Borchers K, Thein R, Sterner-Kock A. Pathogenesis of equine herpesvirus-associated neurological disease: a revised explanation.. Equine Vet J 2006;38:283–287.
    doi: 10.2746/042516406776866462pubmed: 16706288google scholar: lookup
  17. Allen GP, Kydd JH, Slater JD, Smith KC. Advances in understanding of the pathogenesis, epidemiology, and immunological control of equid herpesvirus abortion.. Equine infectious diseases VIII Proceedings of the Eighth International Conference, Dubai 23rd-26th 1999:129–146.
  18. Kydd JH, Smith KC, Hannant D, Livesay GJ, Mumford JA. Distribution of equid herpesvirus-1 (EHV-1) in respiratory tract associated lymphoid tissue: implications for cellular immunity.. Equine Vet J 1994;26:470–473.
    doi: 10.1111/j.2042-3306.1994.tb04052.xpubmed: 7889921google scholar: lookup
  19. Kydd JH, Smith KC, Hannant D, Livesay GJ, Mumford JA. Distribution of equid herpesvirus-1 (EHV-1) in the respiratory tract of ponies: implications for vaccination strategies.. Equine Vet J 1994;26:466–469.
    doi: 10.1111/j.2042-3306.1994.tb04051.xpubmed: 7889920google scholar: lookup
  20. Dutta SK, Myrup AC. Infectious center assay of intracellular virus and infective virus titer for equine mononuclear cells infected in vivo and in vitro with equine herpesviruses.. Can J Comp Med 1983;47:64–69.
    pmc: PMC1235886pubmed: 6299486
  21. Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.. Arch Virol 1986;90:111–124.
    doi: 10.1007/BF01314149pubmed: 3015074google scholar: lookup
  22. Tearle JP, Smith KC, Boyle MS, Binns MM, Livesay GJ. Replication of equid herpesvirus-1 (EHV-1) in the testes and epididymides of ponies and venereal shedding of infectious virus.. J Comp Pathol 1996;115:385–397.
    doi: 10.1016/s0021-9975(96)80073-9pubmed: 9004080google scholar: lookup
  23. Allen GP, Breathnach CC. Quantification by real-time PCR of the magnitude and duration of leucocyte-associated viremia in horses infected with neuropathogenic vs. non-neuropathogenic strains of EHV-1.. Equine Vet J 2006;38:252–257.
    doi: 10.2746/042516406776866453pubmed: 16706281google scholar: lookup
  24. Walter J, Balzer HJ, Seeh C, Fey K, Bleul U. Venereal shedding of equid herpesvirus-1 (EHV-1) in naturally infected stallions.. J Vet Intern Med 2012;26:1500–1504.
    doi: 10.1111/j.1939-1676.2012.00997.xpubmed: 22947047google scholar: lookup
  25. Hussey GS, Goehring LS, Lunn DP, Hussey SB, Huang T. Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions.. Vet Res 2013;44:1–15.
    doi: 10.1186/1297-9716-44-118pmc: PMC4028784pubmed: 24308772google scholar: lookup
  26. Hussey SB, Clark R, Lunn KF, Breathnach C, Soboll G. Detection and quantification of equine herpesvirus-1 viremia and nasal shedding by real-time polymerase chain reaction.. J Vet Diagn Invest 2006;18:335–342.
    doi: 10.1177/104063870601800403pubmed: 16921871google scholar: lookup
  27. Goehring LS, Landolt GA, Morley PS. Detection and management of an outbreak of equine herpesvirus type 1 infection and associated neurological disease in a veterinary teaching hospital.. J Vet Intern Med 2010;24:1176–1183.
    doi: 10.1111/j.1939-1676.2010.0558.xpubmed: 20584137google scholar: lookup
  28. Goehring LS, Van Maanen C, Berendsen M, Cullinane A, de Groot RJ. Experimental infection with neuropathogenic equid herpesvirus type 1 (EHV-1) in adult horses.. Vet J 2010;186:180–187.
    doi: 10.1016/j.tvjl.2009.08.007pubmed: 19726209google scholar: lookup
  29. Gardiner DW, Lunn DP, Goehring LS, Chiang Y-W, Cook C. Strain impact on equine herpesvirus type 1 (EHV-1) abortion models: viral loads in fetal and placental tissues and foals.. Vaccine 2012;30:6564–6572.
    doi: 10.1016/j.vaccine.2012.08.046pubmed: 22944628google scholar: lookup
  30. Smith KC, Borchers K. A study of the pathogenesis of equid herpesvirus-1 (EHV-1) abortion by DNA in-situ hybridization.. J Comp Pathol 2001;125:304–310.
    doi: 10.1053/jcpa.2001.0513pubmed: 11798247google scholar: lookup
  31. Goodman LB, Loregian A, Perkins GA, Nugent J, Buckles EL. A point mutation in A herpesvirus polymerase determines neuropathogenicity.. PLoS Pathog 2007;3:e160.
    doi: 10.1371/journal.ppat.0030160pmc: PMC2065875pubmed: 17997600google scholar: lookup
  32. Allen GP. Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses.. Am J Vet Res 2008;69:1595–1600.
    doi: 10.2460/ajvr.69.12.1595pubmed: 19046006google scholar: lookup
  33. Holz CL, Nelli RK, Wilson ME, Zarski LM, Azab W. Viral genes and cellular markers associated with neurological complications during herpesvirus infections.. J Gen Virol 2017;98:1439–1454.
    doi: 10.1099/jgv.0.000773pubmed: 28631601google scholar: lookup
  34. Gibson JS, Slater JD, Awan AR, Field HJ. Pathogenesis of equine herpesvirus-1 in specific pathogen-free foals: primary and secondary infections and reactivation.. Arch Virol 1992;123:351–366.
    doi: 10.1007/BF01317269pubmed: 1314051google scholar: lookup
  35. Goehring LS, van Winden SC, van Maanen C, Sloet van Oldruitenborgh-Oosterbaan MM. Equine herpesvirus type 1-associated myeloencephalopathy in the Netherlands: a four-year retrospective study (1999-2003). J Vet Intern Med 2006;20:601–607.
    doi: 10.1892/0891-6640(2006)20[601:ehtami]2.0.co;2pubmed: 16734096google scholar: lookup
  36. Klouth E, Zablotski Y, Goehring LS. Apparent breed predilection for equid herpesvirus-1-associated myeloencephalopathy (EHM) in a multiple-breed herd.. Pathogens 2021;10:537.
    doi: 10.3390/pathogens10050537pmc: PMC8145278pubmed: 33947126google scholar: lookup
  37. Crowhurst FA, Dickinson G, Burrows R. An outbreak of paresis in mares and geldings associated with equid herpesvirus 1.. Vet Rec 1981;109:527–528.
    pubmed: 6280366
  38. Maxwell LK, Bentz BG, Gilliam LL, Ritchey JW, Pusterla N. Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-1 infection in horses.. Am J Vet Res 2017;78:1126–1139.
    doi: 10.2460/ajvr.78.10.1126pmc: PMC6440545pubmed: 28945127google scholar: lookup
  39. Hansen S, Baptiste KE, Fjeldborg J, Horohov DW. A review of the equine age-related changes in the immune system: comparisons between human and equine aging, with focus on lung-specific immune-aging.. Ageing Res Rev 2015;20:11–23.
    doi: 10.1016/j.arr.2014.12.002pubmed: 25497559google scholar: lookup
  40. Smith KC, Mumford JA, Lakhani K. A comparison of equid herpesvirus-1 (EHV-1) vascular lesions in the early versus late pregnant equine uterus.. J Comp Pathol 1996;114:231–247.
    doi: 10.1016/s0021-9975(96)80045-4pubmed: 8762581google scholar: lookup
  41. Smith DJ, Hamblin AS, Edington N. Infection of endothelial cells with equine herpesvirus-1 (EHV-1) occurs where there is activation of putative adhesion molecules: a mechanism for transfer of virus.. Equine Vet J 2001;33:138–142.
    doi: 10.1111/j.2042-3306.2001.tb00591.xpubmed: 11266062google scholar: lookup
  42. Bridges CG, Edington N. Innate immunity during Equid herpesvirus 1 (EHV-1) infection.. Clin Exp Immunol 1986;65:172–181.
    pmc: PMC1542268pubmed: 2431815
  43. Gryspeerdt AC, Vandekerckhove AP, Garré B, Barbé F, Van de Walle GR. Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses.. Vet Microbiol 2010;142:242–253.
    doi: 10.1016/j.vetmic.2009.10.015pubmed: 19926232google scholar: lookup
  44. Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H. Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity.. BMC Vet Res 2018;14:1–15.
    doi: 10.1186/s12917-018-1563-4pmc: PMC6106926pubmed: 30134896google scholar: lookup
  45. Zhao J, Poelaert KCK, Van Cleemput J, Nauwynck HJ. CCL2 and CCL5 driven attraction of CD172a+ monocytic cells during an equine herpesvirus type 1 (EHV-1) infection in equine nasal mucosa and the impact of two migration inhibitors, rosiglitazone (RSG) and quinacrine (QC). Vet Res 2017;48:14.
    doi: 10.1186/s13567-017-0419-4pmc: PMC5327560pubmed: 28241864google scholar: lookup
  46. Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Soboll Hussey G. Abortigenic but not neurotropic equine herpes virus 1 modulates the interferon antiviral defense.. Front Cell Infect Microbiol 2018;8:312.
    doi: 10.3389/fcimb.2018.00312pmc: PMC6144955pubmed: 30258819google scholar: lookup
  47. Poelaert KCK, Van Cleemput J, Laval K, Xie J, Favoreel HW. Equine herpesvirus 1 infection orchestrates the expression of chemokines in equine respiratory epithelial cells.. J Gen Virol 2019;100:1567–1579.
    doi: 10.1099/jgv.0.001317pubmed: 31490114google scholar: lookup
  48. Hussey GS, Ashton LV, Quintana AM, Van de Walle GR, Osterrieder N. Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial cells.. Virology 2014;464:76–86.
    doi: 10.1016/j.virol.2014.05.023pubmed: 25046270google scholar: lookup
  49. Soboll Hussey G, Ashton LV, Quintana AM, Lunn DP, Goehring LS. Innate immune responses of airway epithelial cells to infection with equine herpesvirus-1.. Vet Microbiol 2014;170:28–38.
    doi: 10.1016/j.vetmic.2014.01.018pubmed: 24560592google scholar: lookup
  50. Kamel M, Pavulraj S, Osterrieder K, Azab W. EHV-1 pathogenesis: current in vitro models and future perspectives.. Front Vet Sci 2019;6:251.
    doi: 10.3389/fvets.2019.00251pmc: PMC6684782pubmed: 31417917google scholar: lookup
  51. Soboll G, Horohov DW, Aldridge BM, Olsen CW, McGregor MW. Regional antibody and cellular immune responses to equine influenza virus infection, and particle mediated DNA vaccination.. Vet Immunol Immunopathol 2003;94:47–62.
    doi: 10.1016/s0165-2427(03)00060-6pubmed: 12842611google scholar: lookup
  52. Pease A, Behan A, Bohart G. Ultrasound-guided cervical centesis to obtain cerebrospinal fluid in the standing horse.. Vet Radiol Ultrasound 2012;53:92–95.
    doi: 10.1111/j.1740-8261.2011.01855.xpubmed: 21831242google scholar: lookup
  53. Mayhew IG, deLahunta A, Whitlock RH, Krook L, Tasker JB. Spinal cord disease in the horse.. Cornell Vet 1978;68:1–207.
    pubmed: 618720
  54. Mayhew IG. Large Animal Neurology, 2nd ed.. 2009.
  55. Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses.. Vet Immunol Immunopathol 2009;127:242–248.
    doi: 10.1016/j.vetimm.2008.10.313pubmed: 19027964google scholar: lookup
  56. 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.
    doi: 10.3389/fvets.2021.674850pmc: PMC8224402pubmed: 34179166google scholar: lookup
  57. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.. Methods 2001;25:402–408.
    doi: 10.1006/meth.2001.1262pubmed: 11846609google scholar: lookup
  58. Soboll G, Hussey SB, Whalley JM, Allen GP, Koen MT. Antibody and cellular immune responses following DNA vaccination and EHV-1 infection of ponies.. Vet Immunol Immunopathol 2006;111:81–95.
    doi: 10.1016/j.vetimm.2006.01.011pubmed: 16549215google scholar: lookup
  59. Lunn DP, Holmes MA, Schram B, Duffus WP. Monoclonal antibodies specific for equine IgG sub-isotypes including an antibody which recognizes B lymphocytes.. Vet Immunol Immunopathol 1995;47:239–251.
    doi: 10.1016/0165-2427(95)97067-jpubmed: 8571544google scholar: lookup
  60. Sheoran AS, Lunn DP, Holmes MA. Monoclonal antibodies to subclass-specific antigenic determinants on equine immunoglobulin gamma chains and their characterization.. Vet Immunol Immunopathol 1998;62:153–165.
    doi: 10.1016/s0165-2427(97)00162-1pubmed: 9638859google scholar: lookup
  61. Marenzoni ML, De Waure C, Timoney PJ. Efficacy of vaccination against equine herpesvirus type 1 (EHV-1) infection: systematic review and meta-analysis of randomised controlled challenge trials.. Equine Vet J 2023;55:389–404.
    doi: 10.1111/evj.13870pubmed: 35946376google scholar: lookup
  62. Osterrieder K, Dorman DC, Burgess BA, Goehring LS, Gross P. Vaccination for the prevention of equine herpesvirus-1 disease in domesticated horses: a systematic review and meta-analysis.. J Vet Intern Med 2023.
    doi: 10.1111/jvim.16895pmc: PMC11099739pubmed: 37930113google scholar: lookup
  63. Goodman LB, Wagner B, Flaminio MJBF, Sussman KH, Metzger SM. Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1). Vaccine 2006;24:3636–3645.
    doi: 10.1016/j.vaccine.2006.01.062pubmed: 16513225google scholar: lookup
  64. Soboll-Hussey G, Dorman DC, Burgess BA, Goehring L, Gross P. Relationship between equine herpesvirus-1 viremia and abortion or equine herpesvirus myeloencephalopathy in domesticated horses: a systematic review.. J Vet Intern Med 2023.
    doi: 10.1111/jvim.16948pmc: PMC11099755pubmed: 38069576google scholar: lookup
  65. Hussey GS, Hussey SB, Wagner B, Horohov DW, Van de Walle GR. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011;42:1–12.
    doi: 10.1186/1297-9716-42-23pmc: PMC3045331pubmed: 21314906google scholar: lookup
  66. Sutton GA, Viel L, Carman PS, Boag BL. Pathogenesis and clinical signs of equine herpesvirus-1 in experimentally infected ponies in vivo.. Can J Vet Res 1998;62:49–55.
    pmc: PMC1189442pubmed: 9442940
  67. Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H. 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:e0206679.
    doi: 10.1371/journal.pone.0206679pmc: PMC6237298pubmed: 30440016google scholar: lookup
  68. Gibson JS, Slater JD, Field HJ. The pathogenicity of Ab4p, the sequenced strain of equine herpesvirus-1, in specific pathogen-free foals.. Virology 1992;189:317–319.
    doi: 10.1016/0042-6822(92)90707-vpubmed: 1318607google scholar: lookup
  69. Chong YC, Duffus WP. Immune responses of specific pathogen free foals to EHV-1 infection.. Vet Microbiol 1992;32:215–228.
    doi: 10.1016/0378-1135(92)90146-kpubmed: 1280876google scholar: lookup
  70. Edington N, Bridges CG, Griffiths L. Equine interferons following exposure to equid herpesvirus-1 or -4.. J Interferon Res 1989;9:389–392.
    doi: 10.1089/jir.1989.9.389pubmed: 2474039google scholar: lookup
  71. Perkins G, Babasyan S, Stout AE, Freer H, Rollins A. Intranasal IgG4/7 antibody responses protect horses against equid herpesvirus-1 (EHV-1) infection including nasal virus shedding and cell-associated viremia.. Virology 2019;531:219–232.
    doi: 10.1016/j.virol.2019.03.014pubmed: 30928700google scholar: lookup
  72. Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL. An equine herpesvirus type 1 (EHV-1) Ab4 open reading frame 2 deletion mutant provides immunity and protection from EHV-1 infection and disease.. J Virol 2019;93:1–17.
    doi: 10.1128/JVI.01011-19pmc: PMC6819910pubmed: 31462575google scholar: lookup
  73. Soboll Hussey G, Ashton LV, Quintana AM, Van de Walle GR, Osterrieder N. Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial cells.. Virology 2014;464–465:76–86.
    doi: 10.1016/j.virol.2014.05.023pubmed: 25046270google scholar: lookup
  74. Randall RE, Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.. J Gen Virol 2008;89:1–47.
    doi: 10.1099/vir.0.83391-0pubmed: 18089727google scholar: lookup
  75. Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system.. Nat Immunol 2015;16:343–353.
    doi: 10.1038/ni.3123pmc: PMC4507498pubmed: 25789684google scholar: lookup
  76. O’Neill T, Kydd JH, Allen GP, Wattrang E, Mumford JA. Determination of equid herpesvirus 1-specific, CD8+, cytotoxic T lymphocyte precursor frequencies in ponies.. Vet Immunol Immunopathol 1999;70:43–54.
    doi: 10.1016/s0165-2427(99)00037-9pubmed: 10507286google scholar: lookup
  77. Kydd JH, Wattrang E, Hannant D. Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T lymphocytes correlate with protection against abortion following experimental infection of pregnant mares.. Vet Immunol Immunopathol 2003;96:207–217.
    doi: 10.1016/j.vetimm.2003.08.004pubmed: 14592733google scholar: lookup
  78. Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells.. Nat Rev Immunol 2010;10:170–181.
    doi: 10.1038/nri2711pubmed: 20154735google scholar: lookup
  79. Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.. Nat Rev Immunol 2006;6:644–658.
    doi: 10.1038/nri1900pubmed: 16932750google scholar: lookup
  80. Sarkar S, Balasuriya UBR, Horohov DW, Chambers TM. Equine herpesvirus-1 suppresses type-I interferon induction in equine endothelial cells.. Vet Immunol Immunopathol 2015;167:122–129.
    doi: 10.1016/j.vetimm.2015.07.015pubmed: 26275803google scholar: lookup
  81. Oladunni FS, Sarkar S, Reedy S, Balasuriya UBR, Horohov DW. Absence of relationship between type-I interferon suppression and neuropathogenicity of EHV-1.. Vet Immunol Immunopathol 2018;197:24–30.
    doi: 10.1016/j.vetimm.2018.01.007pubmed: 29475503google scholar: lookup
  82. Hussey GS, Giessler KS. Contribution of the immune response to the pathogenesis of equine herpesvirus-1 (EHV-1): are there immune correlates that predict increased risk or protection from EHV-1 myeloencephalopathy?. Vet J 2022;282:105827.
    doi: 10.1016/j.tvjl.2022.105827pubmed: 35405348google scholar: lookup
  83. Wagner B, Burton A, Ainsworth D. Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals.. Vet Res 2010;41:47.
    doi: 10.1051/vetres/2010019pmc: PMC2865874pubmed: 20374696google scholar: lookup
  84. Manickan E, Rouse RJ, Yu Z, Wire WS, Rouse BT. Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes.. J Immunol 1995;155:259–265.
    pubmed: 7602102
  85. Fischer T, Büttner M, Rziha HJ. T helper 1-type cytokine transcription in peripheral blood mononuclear cells of pseudorabies virus (Suid herpesvirus 1)-primed swine indicates efficient immunization.. Immunology 2000;101:378–387.
    doi: 10.1046/j.1365-2567.2000.00124.xpmc: PMC2327083pubmed: 11106942google scholar: lookup
  86. Sin JI, Kim JJ, Boyer JD, Ciccarelli RB, Higgins TJ. In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model.. J Virol 1999;73:501–509.
    doi: 10.1128/JVI.73.1.501-509.1999pmc: PMC103857pubmed: 9847356google scholar: lookup
  87. Abdul K, Abbas A, Shiv P. Cellular and Molecular Immunology.. 2015.
  88. Paillot R, Daly JM, Juillard V, Minke JM, Hannant D. Equine interferon gamma synthesis in lymphocytes after in vivo infection and in vitro stimulation with EHV-1.. Vaccine 2005;23:4541–4551.
    doi: 10.1016/j.vaccine.2005.03.048pubmed: 15913852google scholar: lookup
  89. Paillot R, Ellis SA, Daly JM, Audonnet JC, Minke JM. Characterisation of CTL and IFN-gamma synthesis in ponies following vaccination with a NYVAC-based construct coding for EHV-1 immediate early gene, followed by challenge infection.. Vaccine 2006;24:1490–1500.
    doi: 10.1016/j.vaccine.2005.10.019pubmed: 16269205google scholar: lookup
  90. Breathnach CC, Soboll G, Suresh M, Lunn DP. Equine herpesvirus-1 infection induces IFN-gamma production by equine T lymphocyte subsets.. Vet Immunol Immunopathol 2005;103:207–215.
    doi: 10.1016/j.vetimm.2004.09.024pubmed: 15621307google scholar: lookup
  91. Woolums AR, Siger L, Johnson S, Gallo G, Conlon J. Rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or modified-live and killed BHV-1 is associated with virus-specific interferon gamma production.. Vaccine 2003;21:1158–1164.
    doi: 10.1016/s0264-410x(02)00560-1pubmed: 12559793google scholar: lookup
  92. Coombs DK, Patton T, Kohler AK, Soboll G, Breathnach C. Cytokine responses to EHV-1 infection in immune and non-immune ponies.. Vet Immunol Immunopathol 2006;111:109–116.
    doi: 10.1016/j.vetimm.2006.01.013pubmed: 16473413google scholar: lookup
  93. Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG. Identification of host factors associated with the development of equine herpesvirus myeloencephalopathy by transcriptomic analysis of peripheral blood mononuclear cells from horses.. Viruses 2021;13:1–35.
    doi: 10.3390/v13030356pmc: PMC7995974pubmed: 33668216google scholar: lookup
  94. Wimer CL, Damiani A, Osterrieder N, Wagner B. Equine herpesvirus type-1 modulates CCL2, CCL3, CCL5, CXCL9, and CXCL10 chemokine expression.. Vet Immunol Immunopathol 2011;140:266–274.
    doi: 10.1016/j.vetimm.2011.01.009pubmed: 21349590google scholar: lookup
  95. Wuest TR, Carr DJ. The role of chemokines during herpes simplex virus-1 infection.. Front Biosci 2008;13:4862–4872.
    doi: 10.2741/3045pmc: PMC2430744pubmed: 18508551google scholar: lookup
  96. Dos Santos AC, Barsante MM, Arantes RME, Bernard CCA, Teixeira MM. CCL2 and CCL5 mediate leukocyte adhesion in experimental autoimmune encephalomyelitis--an intravital microscopy study.. J Neuroimmunol 2005;162:122–129.
    doi: 10.1016/j.jneuroim.2005.01.020pubmed: 15833367google scholar: lookup
  97. Vilela MC, Mansur DS, Lacerda-Queiroz N, Rodrigues DH, Lima GK. The chemokine CCL5 is essential for leukocyte recruitment in a model of severe Herpes simplex encephalitis.. Ann N Y Acad Sci 2009;1153:256–263.
    doi: 10.1111/j.1749-6632.2008.03959.xpubmed: 19236348google scholar: lookup
  98. Charan S, Palmer K, Chester P, Mire-Sluis AR, Meager A. Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse.. Immunology 1997;90:586–591.
    doi: 10.1046/j.1365-2567.1997.00202.xpmc: PMC1456683pubmed: 9176113google scholar: lookup
  99. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor.. Annu Rev Immunol 2001;19:683–765.
    doi: 10.1146/annurev.immunol.19.1.683pubmed: 11244051google scholar: lookup
  100. Wagner B, Hillegas JM, Brinker DR, Horohov DW, Antczak DF. Characterization of monoclonal antibodies to equine interleukin-10 and detection of T regulatory 1 cells in horses.. Vet Immunol Immunopathol 2008;122:57–64.
    doi: 10.1016/j.vetimm.2007.10.012pubmed: 18061278google scholar: lookup
  101. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection.. J Immunol 2008;180:5771–5777.
    doi: 10.4049/jimmunol.180.9.5771pubmed: 18424693google scholar: lookup
  102. Waldron P. New test predicts horse’s risk of contracting EHV-1 in an outbreak: College of Veterinary Medicine. 2019. https://www.vet.cornell.edu/news/20191217/new-test-predicts-horse-s-risk-contracting-ehv-1-outbreak
  103. Fermaglich DH, Horohov DW. The effect of aging on immune responses.. Vet Clin North Am Equine Pract 2002;18:621–630.
    doi: 10.1016/s0749-0739(02)00027-5pubmed: 12516937google scholar: lookup
  104. DeNotta S, McFarlane D. Immunosenescence and inflammaging in the aged horse.. Immun Ageing 2023;20:1–10.
    doi: 10.1186/s12979-022-00325-5pmc: PMC9817422pubmed: 36609345google scholar: lookup
  105. Vukmanovic-Stejic M, Sandhu D, Seidel JA, Patel N, Sobande TO. The Characterization of Varicella Zoster Virus-Specific T Cells in Skin and Blood during Aging.. J Invest Dermatol 2015;135:1752–1762.
    doi: 10.1038/jid.2015.63pmc: PMC4471118pubmed: 25734814google scholar: lookup
  106. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone.. FEMS Immunology & Medical Microbiology 2003;38:13–22.
    doi: 10.1016/S0928-8244(03)00202-5pubmed: 12900050google scholar: lookup
  107. González DA, Díaz BB, Rodríguez Pérez M del C, Hernández AG, Chico BND. Sex hormones and autoimmunity.. Immunol Lett 2010;133:6–13.
    doi: 10.1016/j.imlet.2010.07.001pubmed: 20637236google scholar: lookup
  108. Klouth E, Zablotski Y, Petersen JL, de Bruijn M, Gröndahl G. Epidemiological aspects of Equid Herpesvirus-associated Myeloencephalopathy (EHM) outbreaks.. Viruses 2022;14:2576.
    doi: 10.3390/v14112576pmc: PMC9695031pubmed: 36423188google scholar: lookup
  109. Mun-Bryce S, Rosenberg GA. Matrix metalloproteinases in cerebrovascular disease.. J Cereb Blood Flow Metab 1998;18:1163–1172.
    doi: 10.1097/00004647-199811000-00001pubmed: 9809504google scholar: lookup
  110. Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke.. Stroke 2003;34:40–46.
    pubmed: 12511748
  111. Heo JH, Lucero J, Abumiya T, Koziol JA, Copeland BR. Matrix metalloproteinases increase very early during experimental focal cerebral ischemia.. J Cereb Blood Flow Metab 1999;19:624–633.
    doi: 10.1097/00004647-199906000-00005pubmed: 10366192google scholar: lookup
  112. Montaner J, Molina CA, Monasterio J, Abilleira S, Arenillas JF. Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke.. Circulation 2003;107:598–603.
    doi: 10.1161/01.cir.0000046451.38849.90pubmed: 12566373google scholar: lookup
  113. Szóstek-Mioduchowska AZ, Baclawska A, Rebordão MR, Ferreira-Dias G, Skarzynski DJ. Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts.. Theriogenology 2020;153:74–84.
    doi: 10.1016/j.theriogenology.2020.04.040pubmed: 32442743google scholar: lookup
  114. Goehring LS, Soboll Hussey G, Gomez Diez M, Benedict K, Maxwell LK. Plasma D-dimer concentrations during experimental EHV-1 infection of horses.. J Vet Intern Med 2013;27:1535–1542.
    doi: 10.1111/jvim.12203pubmed: 24112533google scholar: lookup
  115. Yeo WM, Osterrieder N, Stokol T. Equine herpesvirus type 1 infection induces procoagulant activity in equine monocytes.. Vet Res 2013;44:16.
    doi: 10.1186/1297-9716-44-16pmc: PMC3618259pubmed: 23497076google scholar: lookup
  116. Stokol T, Serpa PBS, Zahid MN, Brooks MB. Unfractionated and low-molecular-weight heparin and the phosphodiesterase inhibitors, IBMX and cilostazol, block ex vivo equid herpesvirus type-1-induced platelet activation.. Front Vet Sci 2016;3:99.
    doi: 10.3389/fvets.2016.00099pmc: PMC5112437pubmed: 27909693google scholar: lookup
  117. Wilson ME, Holz CL, Kopec AK, Dau JJ, Luyendyk JP. Coagulation parameters following equine herpesvirus type 1 infection in horses.. Equine Vet J 2019;51:102–107.
    doi: 10.1111/evj.12843pubmed: 29658149google scholar: lookup
  118. Stokol T, Yeo WM, Burnett D, DeAngelis N, Huang T. Equid herpesvirus type 1 activates platelets.. PLoS One 2015;10:e0122640.
    doi: 10.1371/journal.pone.0122640pmc: PMC4407896pubmed: 25905776google scholar: lookup
  119. Bonnefoy A, Moura R, Hoylaerts MF. The evolving role of thrombospondin-1 in hemostasis and vascular biology.. Cell Mol Life Sci 2008;65:713–727.
    doi: 10.1007/s00018-007-7487-ypmc: PMC11131602pubmed: 18193161google scholar: lookup
  120. Al Qawasmeh M, Alhusban A, Alfwaress F. An evaluation of the ability of thrombospondin-1 to predict stroke outcomes and mortality after ischemic stroke.. Int J Neurosci 2020;2020:1–4.
    doi: 10.1080/00207454.2020.1825417pubmed: 32941082google scholar: lookup
  121. Cevik O, Baykal AT, Sener A. Platelets proteomic profiles of acute ischemic stroke patients.. PLoS One 2016;11:e0158287.
    doi: 10.1371/journal.pone.0158287pmc: PMC4919045pubmed: 27336623google scholar: lookup
  122. Go YY, Li Y, Chen Z, Han M, Yoo D. Equine arteritis virus does not induce interferon production in equine endothelial cells: identification of nonstructural protein 1 as a main interferon antagonist.. Biomed Res Int 2014;2014:420658.
    doi: 10.1155/2014/420658pmc: PMC4055586pubmed: 24967365google scholar: lookup
  123. Ainsworth DM, Grünig G, Matychak MB, Young J, Wagner B. Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2003;96:83–91.
    doi: 10.1016/s0165-2427(03)00142-9pubmed: 14522137google scholar: lookup
  124. Oladunni FS, Sarkar S, Reedy S, Balasuriya UBR, Horohov DW. Equid herpesvirus 1 targets the sensitization and induction steps to inhibit the Type I interferon response in equine endothelial cells.. J Virol 2019;93:1–17.
    doi: 10.1128/JVI.01342-19pmc: PMC6854505pubmed: 31511388google scholar: lookup

Citations

This article has been cited 4 times.
  1. Pusterla N, Lawton K, Barnum S, Flynn K, Hankin S, Runk D, Mendonsa E, Doherty T. Management of an Equine Herpesvirus-1 Outbreak During a Multi-Week Equestrian Event. Viruses 2025 Apr 24;17(5).
    doi: 10.3390/v17050608pubmed: 40431620google scholar: lookup
  2. de la Cuesta-Torrado M, Vitale V, Velloso Alvarez A, Neira-Egea P, Diss C, Cuervo-Arango J. The Effect of Vaccination Status on Total Lymphocyte Count in Horses Affected by Equine Herpes Virus-1 Myeloencephalopathy. Animals (Basel) 2025 Apr 1;15(7).
    doi: 10.3390/ani15071019pubmed: 40218411google scholar: lookup
  3. Pusterla N, Lawton K, Barnum S, Ross K, Purcell K. Investigation of an Outbreak of Equine Herpesvirus-1 Myeloencephalopathy in a Population of Aged Working Equids. Viruses 2024 Dec 21;16(12).
    doi: 10.3390/v16121963pubmed: 39772269google scholar: lookup
  4. Hu Y, Zhang SY, Sun WC, Feng YR, Gong HR, Ran DL, Zhang BZ, Liu JH. Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity. Viruses 2024 Sep 16;16(9).
    doi: 10.3390/v16091472pubmed: 39339948google scholar: lookup
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