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PloS one2018; 13(11); e0206679; doi: 10.1371/journal.pone.0206679

The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses.

Abstract: The equine herpesvirus type 1 (EHV-1) ORF1 and ORF71 genes have immune modulatory effects in vitro. Experimental infection of horses using virus mutants with multiple deletions including ORF1 and ORF71 showed promise as vaccine candidates against EHV-1. Here, the combined effects of ORF1 and ORF71 deletions from the neuropathogenic EHV-1 strain Ab4 on clinical disease and host immune response were further explored. Three groups of EHV-1 naïve horses were experimentally infected with the ORF1/71 gene deletion mutant (Ab4ΔORF1/71), the parent Ab4 strain, or remained uninfected. In comparison to Ab4, horses infected with Ab4ΔORF1/71 did not show the initial high fever peak characteristic of EHV-1 infection. Ab4ΔORF1/71 infection had reduced nasal shedding (1/5 vs. 5/5) and, simultaneously, decreased intranasal interferon (IFN)-α, interleukin (IL)-10 and soluble CD14 secretion. However, Ab4 and Ab4ΔORF1/71 infection resulted in comparable viremia, suggesting these genes do not regulate the infection of the mononuclear cells and subsequent viremia. Intranasal and serum anti-EHV-1 antibodies to Ab4ΔORF1/71 developed slightly slower than those to Ab4. However, beyond day 12 post infection (d12pi) serum antibodies in both virus-infected groups were similar and remained increased until the end of the study (d114pi). EHV-1 immunoglobulin (Ig) G isotype responses were dominated by short-lasting IgG1 and long-lasting IgG4/7 antibodies. The IgG4/7 response closely resembled the total EHV-1 specific antibody response. Ex vivo re-stimulation of PBMC with Ab4 resulted in IFN-γ and IL-10 secretion by cells from both infected groups within two weeks pi. Flow cytometric analysis showed that IFN-γ producing EHV-1-specific T-cells were mainly CD8+/IFN-γ+ and detectable from d32pi on. Peripheral blood IFN-γ+ T-cell percentages were similar in both infected groups, albeit at low frequency (~0.1%). In summary, the Ab4ΔORF1/71 gene deletion mutant is less virulent but induced antibody responses and cellular immunity similar to the parent Ab4 strain.
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Publication Date: 2018-11-15 PubMed ID: 30440016PubMed Central: PMC6237298DOI: 10.1371/journal.pone.0206679Google 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 focuses on the impact of deleting the ORF1 and ORF71 genes from the EHV-1 virus on disease symptoms and immune responses in horses, showing a reduction in virulence without compromising the immune response.

Objective

The research aims to study the effects of the deletion of the ORF1 and ORF71 genes from EHV-1 virus strain Ab4 in horses, in terms of clinical disease symptoms and host immune response.

Methods and Results

  • Three groups of horses naive to EHV-1 were subjected to different experimental conditions; one group was infected with the mutant virus (Ab4ΔORF1/71), another one with the monoculture parent Ab4 strain, and the last group remained uninfected.
  • Compared to Ab4, horses infected with Ab4ΔORF1/71 did not show the initial high fever that usually characterizes EHV-1 infection. Not just this, they also had reduced nasal shedding and lower secretion of IFN-α, IL-10, and soluble CD14, immune response mediators, from their noses.
  • Interestingly, both Ab4 and Ab4ΔORF1/71 resulted in comparable viremia, the presence of viral particles in the blood, indicating that these genes do not regulate infection of the mononuclear cells responsible for the level of viremia.

Immune Response

  • The immune response was assessed by monitoring the development of antibodies and their longevity.
  • Intranasal and serum antibodies to Ab4ΔORF1/71 developed more slowly than those to Ab4. However, from day 12 post-infection onwards, serum antibodies in both infected horse groups were similar in amount and maintained high levels until the end of the experiment (day 114 post infection).
  • Analysis also showed that the response was dominated by short acting IgG1 and long-lasting IgG4/7 antibodies, with the latter resembling the total EHV-1 specific antibody response.

Cellular Immunity

  • Cellular immunity was evaluated by analyzing ex-vivo re-stimulation of peripheral blood mononuclear cells (PBMCs).
  • Cells from both infected groups secreted IFN-γ and IL-10 after re-stimulation with Ab4 within two weeks of infection.
  • Flow cytometric analysis revealed that the IFN-γ producing EHV-1-specific T-cells were mainly CD8+/IFN-γ+ and became detectable from day 32 onwards. The percentages of these T-cells in peripheral blood was similar in both infected groups, indicating similar cellular immune response in both cases.

Conclusion

The mutant EHV-1 virus with deleted ORF1 and ORF71 genes (Ab4ΔORF1/71) is less virulent, causing less severe disease symptoms in infected horses compared to the parent strain (Ab4), while still inducing a strong and lasting immune response. This makes it a potential candidate for use in vaccine development against EHV-1.

Cite This Article

APA
Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H, Stout AE, Rollins A, Osterrieder N, Goodman LB, Glaser A, Wagner B. (2018). 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, 13(11), e0206679. https://doi.org/10.1371/journal.pone.0206679

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 11
Pages: e0206679
PII: e0206679

Researcher Affiliations

Wimer, Christine L
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Schnabel, Christiane L
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Perkins, Gillian
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Babasyan, Susanna
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Freer, Heather
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Stout, Alison E
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Rollins, Alicia
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Osterrieder, Nikolaus
  • Institut für Virologie, Freie Universität Berlin, Berlin, Germany.
Goodman, Laura B
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Glaser, Amy
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.

MeSH Terms

  • Animals
  • Antibodies, Viral / metabolism
  • Body Temperature
  • Cytokines / metabolism
  • Female
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / virology
  • Herpesvirus 1, Equid / genetics
  • Herpesvirus 1, Equid / pathogenicity
  • Horse Diseases / immunology
  • Horse Diseases / virology
  • Horses
  • Immunity, Cellular
  • Immunoglobulin G / metabolism
  • Male
  • Mutation
  • Nose / immunology
  • Nose / virology
  • Random Allocation
  • Viral Proteins / genetics
  • Viremia / immunology
  • Viremia / veterinary
  • Virulence
  • Virus Shedding

Conflict of Interest Statement

The authors have declared that no competing interests exist.

References

This article includes 80 references
  1. Lunn DP, Davis-Poynter N, Flaminio MJ, Horohov DW, Osterrieder K, Pusterla N, Townsend HG. Equine herpesvirus-1 consensus statement.. J Vet Intern Med 2009 May-Jun;23(3):450-61.
    doi: 10.1111/j.1939-1676.2009.0304.xpubmed: 19645832google scholar: lookup
  2. 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 Nov;26(6):466-9.
    pubmed: 7889920doi: 10.1111/j.2042-3306.1994.tb04051.xgoogle scholar: lookup
  3. Slater JD, Borchers K, Thackray AM, Field HJ. The trigeminal ganglion is a location for equine herpesvirus 1 latency and reactivation in the horse.. J Gen Virol 1994 Aug;75 ( Pt 8):2007-16.
    doi: 10.1099/0022-1317-75-8-2007pubmed: 8046404google scholar: lookup
  4. Perkins GA, Goodman LB, Tsujimura K, Van de Walle GR, Kim SG, Dubovi EJ, Osterrieder N. Investigation of the prevalence of neurologic equine herpes virus type 1 (EHV-1) in a 23-year retrospective analysis (1984-2007).. Vet Microbiol 2009 Nov 18;139(3-4):375-8.
    doi: 10.1016/j.vetmic.2009.06.033pubmed: 19615831google scholar: lookup
  5. 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 Nov;125(4):304-10.
    doi: 10.1053/jcpa.2001.0513pubmed: 11798247google scholar: lookup
  6. Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.. Arch Virol 1986;90(1-2):111-24.
    pubmed: 3015074doi: 10.1007/bf01314149google scholar: lookup
  7. Rebenko-Moll NM, Liu L, Cardona A, Ransohoff RM. Chemokines, mononuclear cells and the nervous system: heaven (or hell) is in the details.. Curr Opin Immunol 2006 Dec;18(6):683-9.
    doi: 10.1016/j.coi.2006.09.005pubmed: 17010588google scholar: lookup
  8. 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.
    doi: 10.1371/journal.pone.0169072pmc: PMC5207648pubmed: 28045974google scholar: lookup
  9. 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 May-Jun;20(3):601-7.
    pubmed: 16734096doi: 10.1892/0891-6640(2006)20[601:ehtami]2.0.co;2google scholar: lookup
  10. Henninger RW, Reed SM, Saville WJ, Allen GP, Hass GF, Kohn CW, Sofaly C. Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center.. J Vet Intern Med 2007 Jan-Feb;21(1):157-65.
    pubmed: 17338164doi: 10.1892/0891-6640(2007)21[157:oondcb]2.0.co;2google scholar: lookup
  11. Kohn CW, Reed SM, Sofaly CD, Henninger RW, Saville WJ, Allen GP. Transmission of EHV-1 by horses with EHV-1 myeloencephalopathy: implications for biosecurity and review. Clin Tech Equine Pract 2006;5:60–6.
  12. Kydd JH, Townsend HG, Hannant D. The equine immune response to equine herpesvirus-1: the virus and its vaccines.. Vet Immunol Immunopathol 2006 May 15;111(1-2):15-30.
    doi: 10.1016/j.vetimm.2006.01.005pubmed: 16476492google scholar: lookup
  13. Osterrieder N, Van de Walle GR. Pathogenic potential of equine alphaherpesviruses: the importance of the mononuclear cell compartment in disease outcome.. Vet Microbiol 2010 Jun 16;143(1):21-8.
    doi: 10.1016/j.vetmic.2010.02.010pubmed: 20202764google scholar: lookup
  14. Patel JR, Edington N, Mumford JA. Variation in cellular tropism between isolates of equine herpesvirus-1 in foals.. Arch Virol 1982;74(1):41-51.
    pubmed: 6297429doi: 10.1007/bf01320781google scholar: lookup
  15. 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 Nov;26(6):470-3.
    pubmed: 7889921doi: 10.1111/j.2042-3306.1994.tb04052.xgoogle scholar: lookup
  16. Goodman LB, Wagner B, Flaminio MJ, Sussman KH, Metzger SM, Holland R, Osterrieder N. 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 Apr 24;24(17):3636-45.
    doi: 10.1016/j.vaccine.2006.01.062pubmed: 16513225google scholar: lookup
  17. Allen GP. Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses.. Am J Vet Res 2008 Dec;69(12):1595-600.
    doi: 10.2460/ajvr.69.12.1595pubmed: 19046006google scholar: lookup
  18. 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.
    pmc: PMC3272919pubmed: 22205656doi: 10.1128/cvi.05522-11google scholar: lookup
  19. Center for Equine Health. EHV-1 Vaccination. UC Davis, Veterinary Medicine 2017.
  20. Goehring LS, Wagner B, Bigbie R, Hussey SB, Rao S, Morley PS, Lunn DP. Control of EHV-1 viremia and nasal shedding by commercial vaccines.. Vaccine 2010 Jul 19;28(32):5203-11.
    doi: 10.1016/j.vaccine.2010.05.065pubmed: 20538091google scholar: lookup
  21. Wagner B, Goodman LB, Babasyan S, Freer H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Perkins GA. Antibody and cellular immune responses of naïve mares to repeated vaccination with an inactivated equine herpesvirus vaccine.. Vaccine 2015 Oct 13;33(42):5588-5597.
    doi: 10.1016/j.vaccine.2015.09.009pubmed: 26384446google scholar: lookup
  22. Bürki F, Rossmanith W, Nowotny N, Pallan C, Möstl K, Lussy H. Viraemia and abortions are not prevented by two commercial equine herpesvirus-1 vaccines after experimental challenge of horses.. Vet Q 1990 Apr;12(2):80-6.
    pubmed: 2163560doi: 10.1080/01652176.1990.9694249google scholar: lookup
  23. Matsumura T, O'Callaghan DJ, Kondo T, Kamada M. Lack of virulence of the murine fibroblast adapted strain, Kentucky A (KyA), of equine herpesvirus type 1 (EHV-1) in young horses.. Vet Microbiol 1996 Feb;48(3-4):353-65.
    pubmed: 9054131doi: 10.1016/0378-1135(09)59999-3google scholar: lookup
  24. Matsumura T, Kondo T, Sugita S, Damiani AM, O'Callaghan DJ, Imagawa H. An equine herpesvirus type 1 recombinant with a deletion in the gE and gI genes is avirulent in young horses.. Virology 1998 Mar 1;242(1):68-79.
    pubmed: 9501037doi: 10.1006/viro.1997.8984google scholar: lookup
  25. Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011 Feb 7;42(1):23.
    doi: 10.1186/1297-9716-42-23pmc: PMC3045331pubmed: 21314906google scholar: lookup
  26. Ma G, Feineis S, Osterrieder N, Van de Walle GR. Identification and characterization of equine herpesvirus type 1 pUL56 and its role in virus-induced downregulation of major histocompatibility complex class I.. J Virol 2012 Apr;86(7):3554-63.
    doi: 10.1128/JVI.06994-11pmc: PMC3302497pubmed: 22278226google scholar: lookup
  27. Soboll Hussey G, Ashton LV, Quintana AM, Van de Walle GR, Osterrieder N, Lunn DP. Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial cells.. Virology 2014 Sep;464-465:76-86.
    pubmed: 25046270doi: 10.1016/j.virol.2014.05.023google scholar: lookup
  28. Allen GP, Yeargan MR. Use of lambda gt11 and monoclonal antibodies to map the genes for the six major glycoproteins of equine herpesvirus 1.. J Virol 1987 Aug;61(8):2454-61.
    pmc: PMC255669pubmed: 3037108doi: 10.1128/jvi.61.8.2454-2461.1987google scholar: lookup
  29. Whittaker GR, Wheldon LA, Giles LE, Stocks JM, Halliburton IW, Killington RA, Meredith DM. Characterization of the high Mr glycoprotein (gP300) of equine herpesvirus type 1 as a novel glycoprotein with extensive O-linked carbohydrate.. J Gen Virol 1990 Oct;71 ( Pt 10):2407-16.
    doi: 10.1099/0022-1317-71-10-2407pubmed: 2172454google scholar: lookup
  30. Colle CF 3rd, Flowers CC, O'Callaghan DJ. Open reading frames encoding a protein kinase, homolog of glycoprotein gX of pseudorabies virus, and a novel glycoprotein map within the unique short segment of equine herpesvirus type 1.. Virology 1992 Jun;188(2):545-57.
    pubmed: 1316673doi: 10.1016/0042-6822(92)90509-ngoogle scholar: lookup
  31. von Einem J, Wellington J, Whalley JM, Osterrieder K, O'Callaghan DJ, Osterrieder N. The truncated form of glycoprotein gp2 of equine herpesvirus 1 (EHV-1) vaccine strain KyA is not functionally equivalent to full-length gp2 encoded by EHV-1 wild-type strain RacL11.. J Virol 2004 Mar;78(6):3003-13.
    doi: 10.1128/JVI.78.6.3003-3013.2004pmc: PMC353745pubmed: 14990719google scholar: lookup
  32. Wellington JE, Allen GP, Gooley AA, Love DN, Packer NH, Yan JX, Whalley JM. The highly O-glycosylated glycoprotein gp2 of equine herpesvirus 1 is encoded by gene 71.. J Virol 1996 Nov;70(11):8195-8.
    pmc: PMC190901pubmed: 8892952doi: 10.1128/jvi.70.11.8195-8198.1996google scholar: lookup
  33. Telford EA, Watson MS, Perry J, Cullinane AA, Davison AJ. The DNA sequence of equine herpesvirus-4.. J Gen Virol 1998 May;79 ( Pt 5):1197-203.
    doi: 10.1099/0022-1317-79-5-1197pubmed: 9603335google scholar: lookup
  34. Osterrieder N, Kaaden OR, Neubauer A. Structure and function of equine herpesvirus glycoproteins—a review. Proceedings of the 8th International Conference on Equine Infectious Diseases R&W Publications 1999. (pp. 111–118).
  35. Crabb BS, Allen GP, Studdert MJ. Characterization of the major glycoproteins of equine herpesviruses 4 and 1 and asinine herpesvirus 3 using monoclonal antibodies.. J Gen Virol 1991 Sep;72 ( Pt 9):2075-82.
    doi: 10.1099/0022-1317-72-9-2075pubmed: 1716650google scholar: lookup
  36. Fukushi H, Yamaguchi T, Yamada S. Complete genome sequence of equine herpesvirus type 9.. J Virol 2012 Dec;86(24):13822.
    doi: 10.1128/JVI.02607-12pmc: PMC3503125pubmed: 23166237google scholar: lookup
  37. Sun Y, MacLean AR, Aitken JD, Brown SM. The role of the gene 71 product in the life cycle of equine herpesvirus 1.. J Gen Virol 1996 Mar;77 ( Pt 3):493-500.
    doi: 10.1099/0022-1317-77-3-493pubmed: 8601787google scholar: lookup
  38. Smith PM, Kahan SM, Rorex CB, von Einem J, Osterrieder N, O'Callaghan DJ. Expression of the full-length form of gp2 of equine herpesvirus 1 (EHV-1) completely restores respiratory virulence to the attenuated EHV-1 strain KyA in CBA mice.. J Virol 2005 Apr;79(8):5105-15.
    doi: 10.1128/JVI.79.8.5105-5115.2005pmc: PMC1069573pubmed: 15795295google scholar: lookup
  39. Rudolph J, O'Callaghan DJ, Osterrieder N. Cloning of the genomes of equine herpesvirus type 1 (EHV-1) strains KyA and racL11 as bacterial artificial chromosomes (BAC).. J Vet Med B Infect Dis Vet Public Health 2002 Feb;49(1):31-6.
    pubmed: 11911590doi: 10.1046/j.1439-0450.2002.00534.xgoogle scholar: lookup
  40. Rudolph J, Osterrieder N. Equine herpesvirus type 1 devoid of gM and gp2 is severely impaired in virus egress but not direct cell-to-cell spread.. Virology 2002 Feb 15;293(2):356-67.
    pubmed: 11886256doi: 10.1006/viro.2001.1277google scholar: lookup
  41. Marshall KR, Sun Y, Brown SM, Field HJ. An equine herpesvirus-1 gene 71 deletant is attenuated and elicits a protective immune response in mice.. Virology 1997 Apr 28;231(1):20-7.
    pubmed: 9143298doi: 10.1006/viro.1997.8483google scholar: lookup
  42. Animal Health Information. Diseases never reported. WAHID Interface 2016.
  43. Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z, Newton JR, Bowden RJ, Allen GP, Davis-Poynter N. Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks.. J Virol 2006 Apr;80(8):4047-60.
    doi: 10.1128/JVI.80.8.4047-4060.2006pmc: PMC1440451pubmed: 16571821google scholar: lookup
  44. Crowhurst FA, Dickinson G, Burrows R. An outbreak of paresis in mares and geldings associated with equid herpesvirus 1.. Vet Rec 1981 Dec 12;109(24):527-8.
    pubmed: 6280366
  45. 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 Apr 15;140(3-4):266-74.
    doi: 10.1016/j.vetimm.2011.01.009pubmed: 21349590google scholar: lookup
  46. Furr M, Reed S. Neurologic Examination. Equine Neurology 2008. Ames, IA: Blackwell Publishing, pp. 65–76.
  47. Elia G, Decaro N, Martella V, Campolo M, Desario C, Lorusso E, Cirone F, Buonavoglia C. Detection of equine herpesvirus type 1 by real time PCR.. J Virol Methods 2006 Apr;133(1):70-5.
    pubmed: 16309751doi: 10.1016/j.jviromet.2005.10.024google scholar: lookup
  48. Wagner B, Hillegas JM, Babasyan S. Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IgE on subpopulations of IgM+ and IgG1+ B-cells in horses.. Vet Immunol Immunopathol 2012 Apr 15;146(2):125-34.
    doi: 10.1016/j.vetimm.2012.02.007pubmed: 22405681google scholar: lookup
  49. Sheoran AS, Sponseller BT, Holmes MA, Timoney JF. Serum and mucosal antibody isotype responses to M-like protein (SeM) of Streptococcus equi in convalescent and vaccinated horses.. Vet Immunol Immunopathol 1997 Nov;59(3-4):239-51.
    pubmed: 9477475doi: 10.1016/s0165-2427(97)00074-3google scholar: lookup
  50. 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 Jul-Aug;41(4):47.
    doi: 10.1051/vetres/2010019pmc: PMC2865874pubmed: 20374696google scholar: lookup
  51. Perkins GA, Goodman LB, Wimer C, Freer H, Babasyan S, Wagner B. Maternal T-lymphocytes in equine colostrum express a primarily inflammatory phenotype.. Vet Immunol Immunopathol 2014 Oct 15;161(3-4):141-50.
    doi: 10.1016/j.vetimm.2014.07.009pubmed: 25174977google scholar: lookup
  52. Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses.. Vet Immunol Immunopathol 2009 Feb 15;127(3-4):242-8.
    doi: 10.1016/j.vetimm.2008.10.313pubmed: 19027964google scholar: lookup
  53. Wagner B, Ainsworth DM, Freer H. Analysis of soluble CD14 and its use as a biomarker in neonatal foals with septicemia and horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2013 Sep 1;155(1-2):124-8.
    doi: 10.1016/j.vetimm.2013.05.018pubmed: 23810420google scholar: lookup
  54. Smith PM, Kahan SM, Rorex CB, von Einem J, Osterrieder N, O'Callaghan DJ. Expression of the full-length form of gp2 of equine herpesvirus 1 (EHV-1) completely restores respiratory virulence to the attenuated EHV-1 strain KyA in CBA mice.. J Virol 2005 Apr;79(8):5105-15.
    doi: 10.1128/JVI.79.8.5105-5115.2005pmc: PMC1069573pubmed: 15795295google scholar: lookup
  55. Pusterla N, Hussey GS. Equine herpesvirus 1 myeloencephalopathy.. Vet Clin North Am Equine Pract 2014 Dec;30(3):489-506.
    pubmed: 25300635doi: 10.1016/j.cveq.2014.08.006google scholar: lookup
  56. Barbić L, Lojkić I, Stevanović V, Bedeković T, Starešina V, Lemo N, Lojkić M, Madić J. Two outbreaks of neuropathogenic equine herpesvirus type 1 with breed-dependent clinical signs.. Vet Rec 2012 Mar 3;170(9):227.
    pubmed: 22262701doi: 10.1136/vr.100150google scholar: lookup
  57. Gryspeerdt A, Vandekerckhove A, Van Doorsselaere J, Van de Walle G, Nauwynck H. Description of an unusually large outbreak of nervous system disorders caused by equine herpesvirus 1 (EHV1) in 2009 in Belgium. Vlaams Diergeneeskundig Tijdschrift 2011;80:147–53.
  58. Pusterla N, Mapes S, David Wilson W. Prevalence of latent alpha-herpesviruses in Thoroughbred racing horses.. Vet J 2012 Aug;193(2):579-82.
    doi: 10.1016/j.tvjl.2012.01.030pubmed: 22405721google scholar: lookup
  59. Allen GP, Kydd JH, Slater JD, Smith KC. Advances in understanding of the pathogenesis, epidemiology and immunological control of equine herpesvirus abortion. Equine Infect Dis 1999;8:129–46.
  60. 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 Dec 15;96(3-4):207-17.
    pubmed: 14592733doi: 10.1016/j.vetimm.2003.08.004google scholar: lookup
  61. Wagner B, Hillegas JM, Flaminio MJ, Wattrang E. Monoclonal antibodies to equine interferon-alpha (IFN-alpha): new tools to neutralize IFN-activity and to detect secreted IFN-alpha.. Vet Immunol Immunopathol 2008 Oct 15;125(3-4):315-25.
    doi: 10.1016/j.vetimm.2008.05.016pubmed: 18586327google scholar: lookup
  62. Wagner B, Wimer C, Freer H, Osterrieder N, Erb HN. 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 2011 Sep 15;143(1-2):116-24.
    doi: 10.1016/j.vetimm.2011.06.032pubmed: 21764140google scholar: lookup
  63. 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.
    pmc: PMC3868305pubmed: 23772953doi: 10.1089/jir.2012.0130google scholar: lookup
  64. Ushijima Y, Luo C, Kamakura M, Goshima F, Kimura H, Nishiyama Y. Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch.. Virol J 2010 Aug 3;7:179.
    pmc: PMC2922189pubmed: 20682038doi: 10.1186/1743-422x-7-179google scholar: lookup
  65. Berkowitz C, Moyal M, Rösen-Wolff A, Darai G, Becker Y. Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral intraperitoneal pathogenicity to immunocompetent mice.. Arch Virol 1994;134(1-2):73-83.
    pubmed: 8279961doi: 10.1007/bf01379108google scholar: lookup
  66. Kehm R, Rösen-Wolff A, Darai G. Restitution of the UL56 gene expression of HSV-1 HFEM led to restoration of virulent phenotype; deletion of the amino acids 217 to 234 of the UL56 protein abrogates the virulent phenotype.. Virus Res 1996 Jan;40(1):17-31.
    pubmed: 8725118doi: 10.1016/0168-1702(96)80248-6google scholar: lookup
  67. Lewis MJ, Wagner B, Woof JM. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies.. Mol Immunol 2008 Feb;45(3):818-27.
    doi: 10.1016/j.molimm.2007.06.158pmc: PMC2075531pubmed: 17669496google scholar: lookup
  68. Jonsdottir S, Hamza E, Janda J, Rhyner C, Meinke A, Marti E, Svansson V, Torsteinsdottir S. Developing a preventive immunization approach against insect bite hypersensitivity using recombinant allergens: A pilot study.. Vet Immunol Immunopathol 2015 Jul 15;166(1-2):8-21.
    doi: 10.1016/j.vetimm.2015.05.002pubmed: 26004943google scholar: lookup
  69. Perkins GA, Wagner B. The development of equine immunity: Current knowledge on immunology in the young horse.. Equine Vet J 2015 May;47(3):267-74.
    doi: 10.1111/evj.12387pubmed: 25405920google scholar: lookup
  70. Wang T, Welte T. Role of natural killer and Gamma-delta T cells in West Nile virus infection.. Viruses 2013 Sep 20;5(9):2298-310.
    doi: 10.3390/v5092298pmc: PMC3798903pubmed: 24061543google scholar: lookup
  71. Wesch D, Beetz S, Oberg HH, Marget M, Krengel K, Kabelitz D. Direct costimulatory effect of TLR3 ligand poly(I:C) on human gamma delta T lymphocytes.. J Immunol 2006 Feb 1;176(3):1348-54.
    pubmed: 16424161doi: 10.4049/jimmunol.176.3.1348google scholar: lookup
  72. Deetz CO, Hebbeler AM, Propp NA, Cairo C, Tikhonov I, Pauza CD. Gamma interferon secretion by human Vgamma2Vdelta2 T cells after stimulation with antibody against the T-cell receptor plus the Toll-Like receptor 2 agonist Pam3Cys.. Infect Immun 2006 Aug;74(8):4505-11.
    doi: 10.1128/IAI.00088-06pmc: PMC1539635pubmed: 16861636google scholar: lookup
  73. Chen ZW, Letvin NL. Vgamma2Vdelta2+ T cells and anti-microbial immune responses.. Microbes Infect 2003 May;5(6):491-8.
    pmc: PMC2873077pubmed: 12758278doi: 10.1016/s1286-4579(03)00074-1google scholar: lookup
  74. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease.. Annu Rev Immunol 2011;29:71-109.
    pubmed: 21166540doi: 10.1146/annurev-immunol-031210-101312google scholar: lookup
  75. Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells.. Nat Rev Immunol 2010 Mar;10(3):170-81.
    pubmed: 20154735doi: 10.1038/nri2711google scholar: lookup
  76. Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions.. J Leukoc Biol 2004 Feb;75(2):163-89.
    pubmed: 14525967doi: 10.1189/jlb.0603252google scholar: lookup
  77. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection.. J Immunol 2008 May 1;180(9):5771-7.
    pubmed: 18424693doi: 10.4049/jimmunol.180.9.5771google scholar: lookup
  78. Paillot R, Daly JM, Juillard V, Minke JM, Hannant D, Kydd JH. Equine interferon gamma synthesis in lymphocytes after in vivo infection and in vitro stimulation with EHV-1.. Vaccine 2005 Aug 22;23(36):4541-51.
    doi: 10.1016/j.vaccine.2005.03.048pubmed: 15913852google scholar: lookup
  79. Paillot R, Daly JM, Luce R, Montesso F, Davis-Poynter N, Hannant D, Kydd JH. Frequency and phenotype of EHV-1 specific, IFN-gamma synthesising lymphocytes in ponies: the effects of age, pregnancy and infection.. Dev Comp Immunol 2007;31(2):202-14.
    doi: 10.1016/j.dci.2006.05.010pubmed: 16824599google scholar: lookup
  80. 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 Feb 10;103(3-4):207-15.
    doi: 10.1016/j.vetimm.2004.09.024pubmed: 15621307google scholar: lookup

Citations

This article has been cited 16 times.
  1. Guarino C, Larson E, Babasyan S, Rollins A, Joshi LR, Laverack M, Parrilla L, Plocharczyk E, Diel DG, Wagner B. Development of a quantitative COVID-19 multiplex assay and its use for serological surveillance in a low SARS-CoV-2 incidence community. PLoS One 2022;17(1):e0262868.
    doi: 10.1371/journal.pone.0262868pubmed: 35061843google scholar: lookup
  2. Palmer MV, Martins M, Falkenberg S, Buckley A, Caserta LC, Mitchell PK, Cassmann ED, Rollins A, Zylich NC, Renshaw RW, Guarino C, Wagner B, Lager K, Diel DG. Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2. J Virol 2021 May 10;95(11).
    doi: 10.1128/JVI.00083-21pubmed: 33692203google scholar: lookup
  3. 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).
    doi: 10.3390/v12090999pubmed: 32911663google scholar: lookup
  4. Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B. 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 Nov 15;93(22).
    doi: 10.1128/JVI.01011-19pubmed: 31462575google scholar: lookup
  5. Tolnai C, O'Sullivan C, Lőrincz M, Karvouni M, Tenk M, Marosi A, Forgách P, Paszerbovics B, Wagenhoffer Z, Kutasi O. Cellular Immune Response in Horses After West Nile Neuroinvasive Disease. Animals (Basel) 2025 Aug 11;15(16).
    doi: 10.3390/ani15162352pubmed: 40867680google scholar: lookup
  6. Liu D, Zhao X, Wang X. The Genomic Characterization of Equid Alphaherpesviruses: Structure, Function, and Genetic Similarity. Vet Sci 2025 Mar 3;12(3).
    doi: 10.3390/vetsci12030228pubmed: 40266963google scholar: lookup
  7. Wagner B, Schnabel CL, Rollins A. Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4. Vaccines (Basel) 2025 Mar 10;13(3).
    doi: 10.3390/vaccines13030290pubmed: 40266191google scholar: lookup
  8. Pradhan SS, Balena V, Bera BC, Anand T, Khetmalis R, Madhwal A, Kandasamy S, Pavulraj S, Bernela M, Mor P, Tripathi BN, Virmani N. Multiple Gene Deletion Mutants of Equine Herpesvirus 1 Exhibit Strong Protective Efficacy Against Wild Virus Challenge in a Murine Model. Vaccines (Basel) 2025 Jan 8;13(1).
    doi: 10.3390/vaccines13010045pubmed: 39852824google scholar: lookup
  9. Holmes CM, Wagner B. Characterization of Nasal Mucosal T Cells in Horses and Their Response to Equine Herpesvirus Type 1. Viruses 2024 Sep 25;16(10).
    doi: 10.3390/v16101514pubmed: 39459849google scholar: lookup
  10. Holmes CM, Babasyan S, Eady N, Schnabel CL, Wagner B. Immune horses rapidly increase antileukoproteinase and lack type I interferon secretion during mucosal innate immune responses against equine herpesvirus type 1. Microbiol Spectr 2024 Oct 3;12(10):e0109224.
    doi: 10.1128/spectrum.01092-24pubmed: 39162558google scholar: lookup
  11. Jentsch MC, Keilhaue A, Wagner B, Rhyner C, Lübke S, Karagulyan M, Arnold C, Lohmann KL, Schnabel CL. Aspergillus fumigatus binding IgA and IgG1 are increased in bronchoalveolar lavage fluid of horses with neutrophilic asthma. Front Immunol 2024;15:1406794.
    doi: 10.3389/fimmu.2024.1406794pubmed: 38953030google scholar: lookup
  12. Giessler KS, Goehring LS, Jacob SI, Davis A, Esser MM, Lee Y, Zarski LM, Weber PSD, Hussey GS. Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses. J Gen Virol 2024 May;105(5).
    doi: 10.1099/jgv.0.001987pubmed: 38767608google scholar: lookup
  13. Eady NA, Holmes C, Schnabel C, Babasyan S, Wagner B. Equine herpesvirus type 1 (EHV-1) replication at the upper respiratory entry site is inhibited by neutralizing EHV-1-specific IgG1 and IgG4/7 mucosal antibodies. J Virol 2024 Jun 13;98(6):e0025024.
    doi: 10.1128/jvi.00250-24pubmed: 38742875google scholar: lookup
  14. Kreutzfeldt N, Chambers TM, Reedy S, Spann KM, Pusterla N. Effect of dexamethasone on antibody response of horses to vaccination with a combined equine influenza virus and equine herpesvirus-1 vaccine. J Vet Intern Med 2024 Jan-Feb;38(1):424-430.
    doi: 10.1111/jvim.16978pubmed: 38141173google scholar: lookup
  15. Soboll-Hussey G, Dorman DC, Burgess BA, Goehring L, Gross P, Neinast C, Osterrieder K, Pusterla N, Lunn DP. Relationship between equine herpesvirus-1 viremia and abortion or equine herpesvirus myeloencephalopathy in domesticated horses: A systematic review. J Vet Intern Med 2024 May-Jun;38(3):1872-1891.
    doi: 10.1111/jvim.16948pubmed: 38069576google scholar: lookup
  16. Pusterla N, Dorman DC, Burgess BA, Goehring L, Gross M, Osterrieder K, Soboll Hussey G, Lunn DP. Viremia and nasal shedding for the diagnosis of equine herpesvirus-1 infection in domesticated horses. J Vet Intern Med 2024 May-Jun;38(3):1765-1791.
    doi: 10.1111/jvim.16958pubmed: 38069548google scholar: lookup
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