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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.

Funding
This study was supported by the:
  • Grayson-Jockey Club Research Foundation
    • Principle Award Recipient: GiselaSoboll Hussey
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-05-20
2024-06-19
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References

  1. Davison AJ. Evolution of the herpesviruses. Vet Microbiol 2002; 86:69–88 [View Article] [PubMed]
    [Google Scholar]
  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 et al. The order Herpesvirales. Arch Virol 2009; 154:171–177 [View Article] [PubMed]
    [Google Scholar]
  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 [View Article] [PubMed]
    [Google Scholar]
  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 [View Article] [PubMed]
    [Google Scholar]
  6. Pusterla N, Hussey GS, Goehring LS. Equine herpesvirus-1 myeloencephalopathy. Vet Clin North Am Equine Pract 2022; 38:339–362 [View Article] [PubMed]
    [Google Scholar]
  7. Lesté-Lasserre C. Deadly viral outbreak ravages European horses. Science 2021; 371:1297 [View Article] [PubMed]
    [Google Scholar]
  8. Sutton G, Thieulent C, Fortier C, Hue ES, Marcillaud-Pitel C et al. 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 [View Article] [PubMed]
    [Google Scholar]
  9. Traub-Dargatz JL, Pelzel-McCluskey AM, Creekmore LH, Geiser-Novotny S, Kasari TR et al. Case-control study of a multistate equine herpesvirus myeloencephalopathy outbreak. J Vet Intern Med 2013; 27:339–346 [View Article] [PubMed]
    [Google Scholar]
  10. Henninger RW, Reed SM, Saville WJ, Allen GP, Hass GF et al. Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center. J Vet Intern Med 2007; 21:157–165 [View Article] [PubMed]
    [Google Scholar]
  11. 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
  12. Pusterla N, Hussey GS. Equine herpesvirus 1 myeloencephalopathy. In Mealey RH. ed Veterinary Clinics of North America: Equine Practice, New Perspectives in Infectious Diseases vol 30 Elsevier; 2014 pp 489–506 [View Article]
    [Google Scholar]
  13. Lunn DP, Davis-Poynter N, Flaminio MJ, Horohov DW, Osterrieder K et al. Equine herpesvirus-1 consensus statement. J Vet Intern Med 2009; 23:450–461 [View Article] [PubMed]
    [Google Scholar]
  14. 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 [View Article] [PubMed]
    [Google Scholar]
  15. Borchers K, Thein R, Sterner-Kock A. Pathogenesis of equine herpesvirus-associated neurological disease: a revised explanation. Equine Vet J 2006; 38:283–287 [View Article] [PubMed]
    [Google Scholar]
  16. Allen GP, Kydd JH, Slater JD, Smith KC. Advances in understanding of the pathogenesis, epidemiology, and immunological control of equid herpesvirus abortion. In Wernery U, Wade JF, Mumford JA, Kaaden O-R. eds Equine infectious diseases VIII Proceedings of the Eighth International Conference, Dubai 23rd-26th Newmarket: R & W Publications;March 1999 pp 129–146
    [Google Scholar]
  17. 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 [View Article] [PubMed]
    [Google Scholar]
  18. 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 [View Article] [PubMed]
    [Google Scholar]
  19. 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 [PubMed]
    [Google Scholar]
  20. 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 [View Article] [PubMed]
    [Google Scholar]
  21. Tearle JP, Smith KC, Boyle MS, Binns MM, Livesay GJ et al. 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 [View Article] [PubMed]
    [Google Scholar]
  22. 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 [View Article] [PubMed]
    [Google Scholar]
  23. Walter J, Balzer HJ, Seeh C, Fey K, Bleul U et al. Venereal shedding of equid herpesvirus-1 (EHV-1) in naturally infected stallions. J Vet Intern Med 2012; 26:1500–1504 [View Article] [PubMed]
    [Google Scholar]
  24. Hussey GS, Goehring LS, Lunn DP, Hussey SB, Huang T et al. Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions. Vet Res 2013; 44:1–15 [View Article] [PubMed]
    [Google Scholar]
  25. Hussey SB, Clark R, Lunn KF, Breathnach C, Soboll G et al. 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 [View Article] [PubMed]
    [Google Scholar]
  26. 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 [View Article] [PubMed]
    [Google Scholar]
  27. Goehring LS, Van Maanen C, Berendsen M, Cullinane A, de Groot RJ et al. Experimental infection with neuropathogenic equid herpesvirus type 1 (EHV-1) in adult horses. Vet J 2010; 186:180–187 [View Article] [PubMed]
    [Google Scholar]
  28. Gardiner DW, Lunn DP, Goehring LS, Chiang Y-W, Cook C et al. 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 [View Article] [PubMed]
    [Google Scholar]
  29. 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 [View Article] [PubMed]
    [Google Scholar]
  30. Goodman LB, Loregian A, Perkins GA, Nugent J, Buckles EL et al. A point mutation in A herpesvirus polymerase determines neuropathogenicity. PLoS Pathog 2007; 3:e160 [View Article] [PubMed]
    [Google Scholar]
  31. 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 [View Article] [PubMed]
    [Google Scholar]
  32. Holz CL, Nelli RK, Wilson ME, Zarski LM, Azab W et al. Viral genes and cellular markers associated with neurological complications during herpesvirus infections. J Gen Virol 2017; 98:1439–1454 [View Article] [PubMed]
    [Google Scholar]
  33. 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 [View Article] [PubMed]
    [Google Scholar]
  34. 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 [View Article] [PubMed]
    [Google Scholar]
  35. 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 [View Article] [PubMed]
    [Google Scholar]
  36. 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]
    [Google Scholar]
  37. Maxwell LK, Bentz BG, Gilliam LL, Ritchey JW, Pusterla N et al. 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 [View Article] [PubMed]
    [Google Scholar]
  38. 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 [View Article] [PubMed]
    [Google Scholar]
  39. 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 [View Article] [PubMed]
    [Google Scholar]
  40. 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 [View Article] [PubMed]
    [Google Scholar]
  41. Bridges CG, Edington N. Innate immunity during Equid herpesvirus 1 (EHV-1) infection. Clin Exp Immunol 1986; 65:172–181 [PubMed]
    [Google Scholar]
  42. Gryspeerdt AC, Vandekerckhove AP, Garré B, Barbé F, Van de Walle GR et al. 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 [View Article] [PubMed]
    [Google Scholar]
  43. Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H et al. 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 [View Article] [PubMed]
    [Google Scholar]
  44. 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 [View Article] [PubMed]
    [Google Scholar]
  45. Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Soboll Hussey G et al. Abortigenic but not neurotropic equine herpes virus 1 modulates the interferon antiviral defense. Front Cell Infect Microbiol 2018; 8:312 [View Article] [PubMed]
    [Google Scholar]
  46. Poelaert KCK, Van Cleemput J, Laval K, Xie J, Favoreel HW et al. Equine herpesvirus 1 infection orchestrates the expression of chemokines in equine respiratory epithelial cells. J Gen Virol 2019; 100:1567–1579 [View Article] [PubMed]
    [Google Scholar]
  47. Hussey GS, Ashton LV, Quintana AM, Van de Walle GR, Osterrieder N et al. Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial cells. Virology 2014; 464:76–86 [View Article] [PubMed]
    [Google Scholar]
  48. Soboll Hussey G, Ashton LV, Quintana AM, Lunn DP, Goehring LS et al. Innate immune responses of airway epithelial cells to infection with equine herpesvirus-1. Vet Microbiol 2014; 170:28–38 [View Article] [PubMed]
    [Google Scholar]
  49. Kamel M, Pavulraj S, Osterrieder K, Azab W. EHV-1 pathogenesis: current in vitro models and future perspectives. Front Vet Sci 2019; 6:251 [View Article] [PubMed]
    [Google Scholar]
  50. Soboll G, Horohov DW, Aldridge BM, Olsen CW, McGregor MW et al. Regional antibody and cellular immune responses to equine influenza virus infection, and particle mediated DNA vaccination. Vet Immunol Immunopathol 2003; 94:47–62 [View Article] [PubMed]
    [Google Scholar]
  51. 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 [View Article] [PubMed]
    [Google Scholar]
  52. Mayhew IG, deLahunta A, Whitlock RH, Krook L, Tasker JB. Spinal cord disease in the horse. Cornell Vet 1978; 68:1–207 [PubMed]
    [Google Scholar]
  53. Mayhew IG. Large Animal Neurology, 2nd ed Chichester, West Sussex: Wiley-Blackwell Pub; 2009
    [Google Scholar]
  54. 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 [View Article] [PubMed]
    [Google Scholar]
  55. 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 [View Article] [PubMed]
    [Google Scholar]
  56. 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 [View Article] [PubMed]
    [Google Scholar]
  57. Soboll G, Hussey SB, Whalley JM, Allen GP, Koen MT et al. Antibody and cellular immune responses following DNA vaccination and EHV-1 infection of ponies. Vet Immunol Immunopathol 2006; 111:81–95 [View Article] [PubMed]
    [Google Scholar]
  58. 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 [View Article] [PubMed]
    [Google Scholar]
  59. 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 [View Article] [PubMed]
    [Google Scholar]
  60. 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 [View Article] [PubMed]
    [Google Scholar]
  61. Osterrieder K, Dorman DC, Burgess BA, Goehring LS, Gross P et al. Vaccination for the prevention of equine herpesvirus-1 disease in domesticated horses: a systematic review and meta-analysis. J Vet Intern Med 2023 [View Article] [PubMed]
    [Google Scholar]
  62. Goodman LB, Wagner B, Flaminio MJBF, Sussman KH, Metzger SM et al. 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 [View Article] [PubMed]
    [Google Scholar]
  63. Soboll-Hussey G, Dorman DC, Burgess BA, Goehring L, Gross P et al. Relationship between equine herpesvirus-1 viremia and abortion or equine herpesvirus myeloencephalopathy in domesticated horses: a systematic review. J Vet Intern Med 2023 [View Article] [PubMed]
    [Google Scholar]
  64. Hussey GS, Hussey SB, Wagner B, Horohov DW, Van de Walle GR et al. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant. Vet Res 2011; 42:1–12 [View Article] [PubMed]
    [Google Scholar]
  65. 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 [PubMed]
    [Google Scholar]
  66. Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H et al. 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 [View Article] [PubMed]
    [Google Scholar]
  67. 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 [View Article] [PubMed]
    [Google Scholar]
  68. Chong YC, Duffus WP. Immune responses of specific pathogen free foals to EHV-1 infection. Vet Microbiol 1992; 32:215–228 [View Article] [PubMed]
    [Google Scholar]
  69. Edington N, Bridges CG, Griffiths L. Equine interferons following exposure to equid herpesvirus-1 or -4. J Interferon Res 1989; 9:389–392 [View Article] [PubMed]
    [Google Scholar]
  70. Perkins G, Babasyan S, Stout AE, Freer H, Rollins A et al. 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 [View Article] [PubMed]
    [Google Scholar]
  71. Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL et al. 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 [View Article] [PubMed]
    [Google Scholar]
  72. Soboll Hussey G, Ashton LV, Quintana AM, Van de Walle GR, Osterrieder N et al. Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial cells. Virology 2014; 464–465:76–86 [View Article] [PubMed]
    [Google Scholar]
  73. Randall RE, Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 2008; 89:1–47 [View Article] [PubMed]
    [Google Scholar]
  74. Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nat Immunol 2015; 16:343–353 [View Article] [PubMed]
    [Google Scholar]
  75. O’Neill T, Kydd JH, Allen GP, Wattrang E, Mumford JA et al. Determination of equid herpesvirus 1-specific, CD8+, cytotoxic T lymphocyte precursor frequencies in ponies. Vet Immunol Immunopathol 1999; 70:43–54 [View Article] [PubMed]
    [Google Scholar]
  76. 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 [View Article] [PubMed]
    [Google Scholar]
  77. Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10:170–181 [View Article] [PubMed]
    [Google Scholar]
  78. 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 [View Article] [PubMed]
    [Google Scholar]
  79. 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 [View Article] [PubMed]
    [Google Scholar]
  80. Oladunni FS, Sarkar S, Reedy S, Balasuriya UBR, Horohov DW et al. Absence of relationship between type-I interferon suppression and neuropathogenicity of EHV-1. Vet Immunol Immunopathol 2018; 197:24–30 [View Article] [PubMed]
    [Google Scholar]
  81. 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 [View Article] [PubMed]
    [Google Scholar]
  82. 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 [View Article] [PubMed]
    [Google Scholar]
  83. 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]
    [Google Scholar]
  84. 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 [View Article] [PubMed]
    [Google Scholar]
  85. Sin JI, Kim JJ, Boyer JD, Ciccarelli RB, Higgins TJ et al. 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 [View Article] [PubMed]
    [Google Scholar]
  86. Abdul K, Abbas A, Shiv P. Cellular and Molecular Immunology Philadelphia, PA, USA: Saunders Elsevier; 2015
    [Google Scholar]
  87. Paillot R, Daly JM, Juillard V, Minke JM, Hannant D et al. Equine interferon gamma synthesis in lymphocytes after in vivo infection and in vitro stimulation with EHV-1. Vaccine 2005; 23:4541–4551 [View Article] [PubMed]
    [Google Scholar]
  88. Paillot R, Ellis SA, Daly JM, Audonnet JC, Minke JM et al. 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 [View Article] [PubMed]
    [Google Scholar]
  89. 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 [View Article] [PubMed]
    [Google Scholar]
  90. 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 [View Article] [PubMed]
    [Google Scholar]
  91. Coombs DK, Patton T, Kohler AK, Soboll G, Breathnach C et al. Cytokine responses to EHV-1 infection in immune and non-immune ponies. Vet Immunol Immunopathol 2006; 111:109–116 [View Article] [PubMed]
    [Google Scholar]
  92. Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG et al. 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 [View Article] [PubMed]
    [Google Scholar]
  93. 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 [View Article] [PubMed]
    [Google Scholar]
  94. Wuest TR, Carr DJ. The role of chemokines during herpes simplex virus-1 infection. Front Biosci 2008; 13:4862–4872 [View Article] [PubMed]
    [Google Scholar]
  95. Dos Santos AC, Barsante MM, Arantes RME, Bernard CCA, Teixeira MM et al. CCL2 and CCL5 mediate leukocyte adhesion in experimental autoimmune encephalomyelitis--an intravital microscopy study. J Neuroimmunol 2005; 162:122–129 [View Article] [PubMed]
    [Google Scholar]
  96. Vilela MC, Mansur DS, Lacerda-Queiroz N, Rodrigues DH, Lima GK et al. 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 [View Article] [PubMed]
    [Google Scholar]
  97. Charan S, Palmer K, Chester P, Mire-Sluis AR, Meager A et al. 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 [View Article] [PubMed]
    [Google Scholar]
  98. 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 [View Article] [PubMed]
    [Google Scholar]
  99. 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 [View Article] [PubMed]
    [Google Scholar]
  100. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol 2008; 180:5771–5777 [View Article] [PubMed]
    [Google Scholar]
  101. 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
  102. Fermaglich DH, Horohov DW. The effect of aging on immune responses. Vet Clin North Am Equine Pract 2002; 18:621–630 [View Article] [PubMed]
    [Google Scholar]
  103. DeNotta S, McFarlane D. Immunosenescence and inflammaging in the aged horse. Immun Ageing 2023; 20:1–10 [View Article]
    [Google Scholar]
  104. Vukmanovic-Stejic M, Sandhu D, Seidel JA, Patel N, Sobande TO et al. The Characterization of Varicella Zoster Virus-Specific T Cells in Skin and Blood during Aging. J Invest Dermatol 2015; 135:1752–1762 [View Article] [PubMed]
    [Google Scholar]
  105. 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 [View Article]
    [Google Scholar]
  106. González DA, Díaz BB, Rodríguez Pérez M del C, Hernández AG, Chico BND et al. Sex hormones and autoimmunity. Immunol Lett 2010; 133:6–13 [View Article] [PubMed]
    [Google Scholar]
  107. Klouth E, Zablotski Y, Petersen JL, de Bruijn M, Gröndahl G et al. Epidemiological aspects of Equid Herpesvirus-associated Myeloencephalopathy (EHM) outbreaks. Viruses 2022; 14:2576 [View Article] [PubMed]
    [Google Scholar]
  108. Mun-Bryce S, Rosenberg GA. Matrix metalloproteinases in cerebrovascular disease. J Cereb Blood Flow Metab 1998; 18:1163–1172 [View Article] [PubMed]
    [Google Scholar]
  109. Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I et al. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 2003; 34:40–46 [PubMed]
    [Google Scholar]
  110. Heo JH, Lucero J, Abumiya T, Koziol JA, Copeland BR et al. Matrix metalloproteinases increase very early during experimental focal cerebral ischemia. J Cereb Blood Flow Metab 1999; 19:624–633 [View Article] [PubMed]
    [Google Scholar]
  111. Montaner J, Molina CA, Monasterio J, Abilleira S, Arenillas JF et al. Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 2003; 107:598–603 [View Article] [PubMed]
    [Google Scholar]
  112. 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 [View Article] [PubMed]
    [Google Scholar]
  113. Goehring LS, Soboll Hussey G, Gomez Diez M, Benedict K, Maxwell LK et al. Plasma D-dimer concentrations during experimental EHV-1 infection of horses. J Vet Intern Med 2013; 27:1535–1542 [View Article] [PubMed]
    [Google Scholar]
  114. Yeo WM, Osterrieder N, Stokol T. Equine herpesvirus type 1 infection induces procoagulant activity in equine monocytes. Vet Res 2013; 44:16 [View Article] [PubMed]
    [Google Scholar]
  115. 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 [View Article] [PubMed]
    [Google Scholar]
  116. Wilson ME, Holz CL, Kopec AK, Dau JJ, Luyendyk JP et al. Coagulation parameters following equine herpesvirus type 1 infection in horses. Equine Vet J 2019; 51:102–107 [View Article] [PubMed]
    [Google Scholar]
  117. Stokol T, Yeo WM, Burnett D, DeAngelis N, Huang T et al. Equid herpesvirus type 1 activates platelets. PLoS One 2015; 10:e0122640 [View Article] [PubMed]
    [Google Scholar]
  118. 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 [View Article] [PubMed]
    [Google Scholar]
  119. 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 [View Article] [PubMed]
    [Google Scholar]
  120. Cevik O, Baykal AT, Sener A. Platelets proteomic profiles of acute ischemic stroke patients. PLoS One 2016; 11:e0158287 [View Article] [PubMed]
    [Google Scholar]
  121. Go YY, Li Y, Chen Z, Han M, Yoo D et al. 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 [View Article]
    [Google Scholar]
  122. Ainsworth DM, Grünig G, Matychak MB, Young J, Wagner B et al. 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 [View Article]
    [Google Scholar]
  123. Oladunni FS, Sarkar S, Reedy S, Balasuriya UBR, Horohov DW et al. 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 [View Article]
    [Google Scholar]
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