FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Animals (Basel) / Cellular Immune Response in Horses After West Nile Neuroinva...
Animals : an open access journal from MDPI2025; 15(16); 2352; doi: 10.3390/ani15162352

Cellular Immune Response in Horses After West Nile Neuroinvasive Disease.

Abstract: West Nile virus (WNV) is a mosquito-borne neurotropic virus that causes neurologic disease in both humans and horses. Yet the long-term cellular immune response following natural infection in horses remains poorly understood. This study aims to evaluate the WNV-specific T-cell response in horses recovered from West Nile neuroinvasive disease (WNND). Twelve client-owned horses (4 Hungarian sport horses, 2 Lippizaners, 1 KWPN, 1 Shagya Arabian, 1 Friesian, 1 Gidran, 1 Andalusian, and 1 draft cross horse) with confirmed clinical WNV infection were enrolled, and peripheral blood mononuclear cells (PBMCs) were collected approximately 290 days post infection. An equine interferon-gamma (IFNγ) Enzyme-Linked Immunospot (ELISpot) assay was performed using a WNV capsid peptide pool as an antigen to assess virus-specific cellular immunity. Results: Ten of twelve horses (83%) exhibited a significant IFNγ response. Statistical analyses revealed no association between ELISpot responses and clinical severity, age, sex, breed, or neutralizing antibody titers. These results demonstrate that naturally infected horses are capable of mounting robust WNV-specific T-cell responses independent of humoral immunity. The findings support a potentially important role for cellular immune memory in long-term protection against WNV reinfection and suggest that the capsid peptide-based ELISpot assay may serve as a useful diagnostic or research tool for the evaluation of orthoflavivirus immunity in equines.
Get Full Text
Publication Date: 2025-08-11 PubMed ID: 40867680PubMed Central: PMC12383191DOI: 10.3390/ani15162352Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research investigates the long-term T-cell immune response in horses that have recovered from West Nile neuroinvasive disease (WNND), caused by the West Nile virus (WNV), focusing on how their cellular immunity persists approximately 290 days after natural infection.

Background

  • West Nile virus (WNV) is a mosquito-transmitted virus that affects the nervous system of humans and horses, often leading to neuroinvasive disease.
  • While antibody (humoral) responses to WNV in horses are somewhat understood, the long-term cellular immune response, specifically T-cell mediated immunity, has not been thoroughly explored.
  • Cellular immunity involves T cells that can recognize and respond to viral components, which may be important for lasting protection against reinfection.

Study Design and Methods

  • Twelve client-owned horses with naturally confirmed clinical WNV infection participated; these horses represented a variety of breeds including Hungarian sport horses, Lippizaners, KWPN, Shagya Arabian, Friesian, Gidran, Andalusian, and a draft cross horse.
  • Blood samples were taken approximately 290 days (about 9.5 months) post-infection to analyze the horses’ immune cells.
  • Peripheral blood mononuclear cells (PBMCs) were extracted from the blood samples. These include lymphocytes such as T cells and other immune cells.
  • An enzyme-linked immunospot (ELISpot) assay was used, which detects interferon-gamma (IFNγ) – a key cytokine produced by activated T cells.
  • The ELISpot assay used a pool of West Nile virus capsid peptides (small protein fragments) as antigens to stimulate the T cells and measure the virus-specific cellular immune response.

Key Findings

  • 10 out of the 12 horses (83%) showed a significant IFNγ response, indicating the presence of WNV-specific T-cell immunity long after recovery.
  • The study found no correlation between the strength of the T-cell response and factors such as:
    • Clinical severity of the initial WNV infection
    • Age of the horses
    • Sex of the horses
    • Breed
    • Neutralizing antibody titers (levels of circulating antibodies against WNV)
  • These results suggest that the cellular immune response operates independently of the humoral (antibody) immunity.

Implications of the Research

  • The presence of a robust, long-lasting WNV-specific T-cell response supports the idea that cellular immune memory is an important component of protection against potential WNV reinfection in horses.
  • The capsid peptide-based IFNγ ELISpot assay worked well as a tool to measure cellular immunity, showing promise for future diagnostic or research applications.
  • This assay could therefore aid in better understanding and monitoring protective immunity against WNV and possibly other related flaviviruses (orthoflavivirus family) in horses.
  • From a veterinary and epidemiological perspective, understanding cellular immunity can help improve vaccine strategies or immune monitoring after natural infection.

Conclusion

  • Horses naturally infected with WNV develop detectable and durable T-cell responses months after infection.
  • This cellular immunity appears to be maintained regardless of other clinical or demographic factors.
  • The study highlights the potential significance of T-cell-based assays for evaluating immune status against WNV in equine populations.

Cite This Article

APA
Tolnai C, O'Sullivan C, Lőrincz M, Karvouni M, Tenk M, Marosi A, Forgách P, Paszerbovics B, Wagenhoffer Z, Kutasi O. (2025). Cellular Immune Response in Horses After West Nile Neuroinvasive Disease. Animals (Basel), 15(16), 2352. https://doi.org/10.3390/ani15162352

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 15
Issue: 16
PII: 2352

Researcher Affiliations

Tolnai, Csenge
  • Department of Microbiology and Infectious Diseases, University of Veterinary Medicine Budapest, 1143 Budapest, Hungary.
  • Health Safety National Laboratory, 1078 Budapest, Hungary.
O'Sullivan, Ciara
  • Department of Microbiology and Infectious Diseases, University of Veterinary Medicine Budapest, 1143 Budapest, Hungary.
Lőrincz, Márta
  • Department of Microbiology and Infectious Diseases, University of Veterinary Medicine Budapest, 1143 Budapest, Hungary.
  • Health Safety National Laboratory, 1078 Budapest, Hungary.
Karvouni, Maria
  • MABTECH AB, SE-131 52 Nacka Strand, Sweden.
Tenk, Miklós
  • Department of Microbiology and Infectious Diseases, University of Veterinary Medicine Budapest, 1143 Budapest, Hungary.
  • Health Safety National Laboratory, 1078 Budapest, Hungary.
Marosi, András
  • Department of Microbiology and Infectious Diseases, University of Veterinary Medicine Budapest, 1143 Budapest, Hungary.
  • Health Safety National Laboratory, 1078 Budapest, Hungary.
Forgách, Petra
  • Department of Microbiology and Infectious Diseases, University of Veterinary Medicine Budapest, 1143 Budapest, Hungary.
  • Health Safety National Laboratory, 1078 Budapest, Hungary.
Paszerbovics, Bettina
  • Department of Biostatistics, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary.
Wagenhoffer, Zsombor
  • Department of Animal Nutrition and Clinical Dietetics, Institute for Animal Breeding, Nutrition and Laboratory Animal Science, University of Veterinary Medicine Budapest, 1077 Budapest, Hungary.
Kutasi, Orsolya
  • Department of Animal Nutrition and Clinical Dietetics, Institute for Animal Breeding, Nutrition and Laboratory Animal Science, University of Veterinary Medicine Budapest, 1077 Budapest, Hungary.

Grant Funding

  • SRF-001. and SRF-002. / University of Veterinary Medicine Budapest
  • RRF 2.3.1-21-2021-00006. / National Research, Development and Innovation Office

Conflict of Interest Statement

Maria Karvouni was employed by MABTECH AB. All the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 111 references
  1. Sejvar JJ. West Nile Virus: An Historical Overview.. Ochsner J 2003;5:6–10.
    pmc: PMC3111838pubmed: 21765761
  2. Chancey C, Grinev A, Volkova E, Rios M. The Global Ecology and Epidemiology of West Nile Virus.. BioMed Res. Int. 2015;2015:376230.
    doi: 10.1155/2015/376230pmc: PMC4383390pubmed: 25866777google scholar: lookup
  3. Erazo D, Grant L, Ghisbain G, Marini G, Colón-González FJ, Wint W, Rizzoli A, Van Bortel W, Vogels CBF, Grubaugh ND. Contribution of Climate Change to the Spatial Expansion of West Nile Virus in Europe.. Nat. Commun. 2024;15:1196.
    doi: 10.1038/s41467-024-45290-3pmc: PMC10853512pubmed: 38331945google scholar: lookup
  4. Andreychev A, Boyarova E, Nesterova D. Climate Change’s Impact on Recording of West Nile Fever of Animals in the Middle Volga Region.. BIO Web Conf. 2025;181:02023.
    doi: 10.1051/bioconf/202518102023google scholar: lookup
  5. Postler TS, Beer M, Blitvich BJ, Bukh J, de Lamballerie X, Drexler JF, Imrie A, Kapoor A, Karganova GG, Lemey P. Renaming of the Genus Flavivirus to Orthoflavivirus and Extension of Binomial Species Names within the Family Flaviviridae.. Arch. Virol. 2023;168:224.
    doi: 10.1007/s00705-023-05835-1pubmed: 37561168google scholar: lookup
  6. Byas AD, Ebel GD. Comparative Pathology of West Nile Virus in Humans and Non-Human Animals.. Pathogens 2020;9:48.
    doi: 10.3390/pathogens9010048pmc: PMC7168622pubmed: 31935992google scholar: lookup
  7. Bruno L, Nappo MA, Frontoso R, Perrotta MG, Di Lecce R, Guarnieri C, Ferrari L, Corradi A. West Nile Virus (WNV): One-Health and Eco-Health Global Risks.. Vet. Sci. 2025;12:288.
    doi: 10.3390/vetsci12030288pmc: PMC11945822pubmed: 40266979google scholar: lookup
  8. Schwarz ER, Long MT. Comparison of West Nile Virus Disease in Humans and Horses: Exploiting Similarities for Enhancing Syndromic Surveillance.. Viruses 2023;15:1230.
    doi: 10.3390/v15061230pmc: PMC10303507pubmed: 37376530google scholar: lookup
  9. Porter MB, Long MT, Getman LM, Giguère S, MacKay RJ, Lester GD, Alleman AR, Wamsley HL, Franklin RP, Jacks S. West Nile Virus Encephalomyelitis in Horses: 46 Cases (2001). J. Am. Veter. Med Assoc. 2003;222:1241–1247.
    doi: 10.2460/javma.2003.222.1241pubmed: 12725313google scholar: lookup
  10. Kutasi O, Bakonyi T, Lecollinet S, Biksi I, Ferenczi E, Bahuon C, Sardi S, Zientara S, Szenci O. Equine Encephalomyelitis Outbreak Caused by a Genetic Lineage 2 West Nile Virus in Hungary.. Vet. Intern. Med. 2011;25:586–591.
    doi: 10.1111/j.1939-1676.2011.0715.xpubmed: 21457323google scholar: lookup
  11. García-Bocanegra I, Belkhiria J, Napp S, Cano-Terriza D, Jiménez-Ruiz S, Martínez-López B. Epidemiology and Spatio-Temporal Analysis of West Nile Virus in Horses in Spain between 2010 and 2016.. Transbound. Emerg. Dis. 2018;65:567–577.
    doi: 10.1111/tbed.12742pubmed: 29034611google scholar: lookup
  12. de Heus P, Kolodziejek J, Camp JV, Dimmel K, Bagó Z, Hubálek Z, van den Hoven R, Cavalleri J-MV, Nowotny N. Emergence of West Nile Virus Lineage 2 in Europe: Characteristics of the First Seven Cases of West Nile Neuroinvasive Disease in Horses in Austria.. Transbound. Emerg. Dis. 2020;67:1189–1197.
    doi: 10.1111/tbed.13452pmc: PMC7317211pubmed: 31840920google scholar: lookup
  13. Fehér OE, Fehérvári P, Tolnai CH, Forgách P, Malik P, Jerzsele Á, Wagenhoffer Z, Szenci O, Korbacska-Kutasi O. Epidemiology and Clinical Manifestation of West Nile Virus Infections of Equines in Hungary, 2007–2020.. Viruses 2022;14:2551.
    doi: 10.3390/v14112551pmc: PMC9694158pubmed: 36423160google scholar: lookup
  14. Cavalleri J-MV, Korbacska-Kutasi O, Leblond A, Paillot R, Pusterla N, Steinmann E, Tomlinson J. European College of Equine Internal Medicine Consensus Statement on Equine Flaviviridae Infections in Europe.. J. Vet. Intern. Med. 2022;36:1858–1871.
    doi: 10.1111/jvim.16581pmc: PMC9708432pubmed: 36367340google scholar: lookup
  15. Ahlers LRH, Goodman AG. The Immune Responses of the Animal Hosts of West Nile Virus: A Comparison of Insects, Birds, and Mammals.. Front. Cell Infect. Microbiol. 2018;8:96.
    doi: 10.3389/fcimb.2018.00096pmc: PMC5891621pubmed: 29666784google scholar: lookup
  16. Trobaugh D, Green S. Of Mice and Men: Protective and Pathogenic Immune Responses to West Nile Virus Infection. Curr. Trop. Med. Rep. 2015;2:41–48.
    doi: 10.1007/s40475-015-0040-4pmc: PMC4479143pubmed: 26120511google scholar: lookup
  17. Suthar MS, Diamond MS, Gale M Jr. West Nile Virus Infection and Immunity. Nat. Rev. Microbiol. 2013;11:115–128.
    doi: 10.1038/nrmicro2950pubmed: 23321534google scholar: lookup
  18. Netland J, Bevan MJ. CD8 and CD4 T Cells in West Nile Virus Immunity and Pathogenesis. Viruses 2013;5:2573–2584.
    doi: 10.3390/v5102573pmc: PMC3814605pubmed: 24153060google scholar: lookup
  19. Aguilar-Valenzuela R, Netland J, Seo Y-J, Bevan MJ, Grakoui A, Suthar MS. Dynamics of Tissue-Specific CD8+ T Cell Responses during West Nile Virus Infection. J. Virol. 2018;92:e00014-18.
    doi: 10.1128/JVI.00014-18pmc: PMC5923067pubmed: 29514902google scholar: lookup
  20. Shrestha B, Diamond MS. Role of CD8+ T Cells in Control of West Nile Virus Infection. J. Virol. 2004;78:8312–8321.
    doi: 10.1128/JVI.78.15.8312-8321.2004pmc: PMC446114pubmed: 15254203google scholar: lookup
  21. Cho H, Diamond MS. Immune Responses to West Nile Virus Infection in the Central Nervous System. Viruses 2012;4:3812–3830.
    doi: 10.3390/v4123812pmc: PMC3528292pubmed: 23247502google scholar: lookup
  22. Lanteri MC, Diamond MS, Law JP, Chew GM, Wu S, Inglis HC, Wong D, Busch MP, Norris PJ, Ndhlovu LC. Increased Frequency of Tim-3 Expressing T Cells Is Associated with Symptomatic West Nile Virus Infection. PLoS ONE 2014;9:e92134.
    doi: 10.1371/journal.pone.0092134pmc: PMC3958446pubmed: 24642562google scholar: lookup
  23. Klein RS, Lin E, Zhang B, Luster AD, Tollett J, Samuel MA, Engle M, Diamond MS. Neuronal CXCL10 Directs CD8+ T-Cell Recruitment and Control of West Nile Virus Encephalitis. J. Virol. 2005;79:11457–11466.
    doi: 10.1128/JVI.79.17.11457-11466.2005pmc: PMC1193600pubmed: 16103196google scholar: lookup
  24. Brien JD, Uhrlaub JL, Hirsch A, Wiley CA, Nikolich-Žugich J. Key Role of T Cell Defects in Age-Related Vulnerability to West Nile Virus. J. Exp. Med. 2009;206:2735–2745.
    doi: 10.1084/jem.20090222pmc: PMC2806630pubmed: 19901080google scholar: lookup
  25. Read A, Finlaison D, Gu X, Hick P, Moloney B, Wright T, Kirkland P. Clinical and Epidemiological Features of West Nile Virus Equine Encephalitis in New South Wales, Australia, 2011. Aust. Vet. J. 2019;97:133–143.
    doi: 10.1111/avj.12810pubmed: 31025323google scholar: lookup
  26. Cui W, Kaech SM. Generation of Effector CD8+ T Cells and Their Conversion to Memory T Cells. Immunol. Rev. 2010;236:151–166.
    doi: 10.1111/j.1600-065X.2010.00926.xpmc: PMC4380273pubmed: 20636815google scholar: lookup
  27. Kedzierska K, Valkenburg S, Doherty P, Davenport M, Venturi V. Use It or Lose It: Establishment and Persistence of T Cell Memory. Front. Immunol. 2012;3:357.
    doi: 10.3389/fimmu.2012.00357pmc: PMC3515894pubmed: 23230439google scholar: lookup
  28. Saade F, Gorski SA, Petrovsky N. Pushing the Frontiers of T-Cell Vaccines: Accurate Measurement of Human T-Cell Responses. Expert Rev. Vaccines 2012;11:1459–1470.
    doi: 10.1586/erv.12.125pmc: PMC3581609pubmed: 23252389google scholar: lookup
  29. Tolnai CH, Forgách P, Marosi A, Fehér O, Paszerbovics B, Tenk M, Wagenhoffer Z, Kutasi O. Long-Term Humoral Immune Response After West Nile Virus Convalescence in Horses in a Geographic Area of Multiple Orthoflavivirus Co-Circulation. J. Vet. Intern. Med. 2025;39:e70176.
    doi: 10.1111/jvim.70176pmc: PMC12171932pubmed: 40525557google scholar: lookup
  30. Joó K, Bakonyi T, Szenci O, Sárdi S, Ferenczi E, Barna M, Malik P, Hubalek Z, Fehér O, Kutasi O. Comparison of Assays for the Detection of West Nile Virus Antibodies in Equine Serum after Natural Infection or Vaccination. Vet. Immunol. Immunopathol. 2017;183:1–6.
    doi: 10.1016/j.vetimm.2016.10.015pubmed: 28063471google scholar: lookup
  31. Rahav G, Hagin M, Maor Y, Yahalom G, Hindiyeh M, Mendelson E, Bin H. Primary Versus Nonprimary West Nile Virus Infection: A Cohort Study. J. Infect. Dis. 2016;213:755–761.
    doi: 10.1093/infdis/jiv507pubmed: 26508125google scholar: lookup
  32. El Garch H, Minke JM, Rehder J, Richard S, Edlund Toulemonde C, Dinic S, Andreoni C, Audonnet JC, Nordgren R, Juillard V. A West Nile Virus (WNV) Recombinant Canarypox Virus Vaccine Elicits WNV-Specific Neutralizing Antibodies and Cell-Mediated Immune Responses in the Horse. Vet. Immunol. Immunopathol. 2008;123:230–239.
    doi: 10.1016/j.vetimm.2008.02.002pubmed: 18372050google scholar: lookup
  33. Dagur PK, McCoy JP. Collection, Storage, and Preparation of Human Blood Cells. CP Cytom. 2015;73:5.1.1–5.1.16.
    doi: 10.1002/0471142956.cy0501s73pmc: PMC4524540pubmed: 26132177google scholar: lookup
  34. Kuerten S, Batoulis H, Recks MS, Karacsony E, Zhang W, Subbramanian RA, Lehmann PV. Resting of Cryopreserved PBMC Does Not Generally Benefit the Performance of Antigen-Specific T Cell ELISPOT Assays. Cells 2012;1:409–427.
    doi: 10.3390/cells1030409pmc: PMC3901103pubmed: 24710483google scholar: lookup
  35. Moodie Z, Price L, Gouttefangeas C, Mander A, Janetzki S, Löwer M, Welters MJP, Ottensmeier C, van der Burg SH, Britten CM. Response Definition Criteria for ELISPOT Assays Revisited. Cancer Immunol. Immunother. 2010;59:1489–1501.
    doi: 10.1007/s00262-010-0875-4pmc: PMC2909425pubmed: 20549207google scholar: lookup
  36. Moodie Z, Price L, Janetzki S, Britten CM. Response Determination Criteria for ELISPOT: Toward a Standard That Can Be Applied Across Laboratories. 2012. pp. 185–196.
    pubmed: 21956511
  37. Tizard IR. Veterinary Immunology. 11th ed. Elsevier; St. Louis, MA, USA: 2025.
  38. Lanteri MC, Heitman JW, Owen RE, Busch T, Gefter N, Kiely N, Kamel HT, Tobler LH, Busch MP, Norris PJ. Comprehensive Analysis of West Nile Virus–Specific T Cell Responses in Humans. J. Infect. Dis. 2008;197:1296–1306.
    doi: 10.1086/586898pubmed: 18422442google scholar: lookup
  39. Calarota SA, Baldanti F. Enumeration and Characterization of Human Memory T Cells by Enzyme-Linked Immunospot Assays. Clin. Dev. Immunol. 2013;2013:637649.
    doi: 10.1155/2013/637649pmc: PMC3844203pubmed: 24319467google scholar: lookup
  40. Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H, Stout AE, Rollins A, Osterrieder N, Goodman LB, Glaser A. 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
  41. Holmes CM, Wagner B. Characterization of Nasal Mucosal T Cells in Horses and Their Response to Equine Herpesvirus Type 1. Viruses 2024;16:1514.
    doi: 10.3390/v16101514pmc: PMC11512333pubmed: 39459849google scholar: lookup
  42. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an Asthma-like Disease of Horses. Respirology 2011;16:1027–1046.
    doi: 10.1111/j.1440-1843.2011.02033.xpubmed: 21824219google scholar: lookup
  43. Witkowska-Piłaszewicz O, Malin K, Dąbrowska I, Grzędzicka J, Ostaszewski P, Carter C. Immunology of Physical Exercise: Is Equus Caballus an Appropriate Animal Model for Human Athletes?. Int. J. Mol. Sci. 2024;25:5210.
    doi: 10.3390/ijms25105210pmc: PMC11121269pubmed: 38791248google scholar: lookup
  44. Parsons R, Lelic A, Hayes L, Carter A, Marshall L, Evelegh C, Drebot M, Andonova M, McMurtrey C, Hildebrand W. The Memory T Cell Response to West Nile Virus in Symptomatic Humans Following Natural Infection Is Not Influenced by Age and Is Dominated by a Restricted Set of CD8+ T Cell Epitopes1. J. Immunol. 2008;181:1563–1572.
    doi: 10.4049/jimmunol.181.2.1563pubmed: 18606712google scholar: lookup
  45. Felippe MJB. Equine Clinical Immunology. John Wiley & Sons, Inc; Ames, IA, USA: West Sussex, UK: 2016.
  46. Horohov DW, Adams AA, Chambers TM. Immunosenescence of the Equine Immune System. J. Comp. Pathol. 2010;142:S78–S84.
    doi: 10.1016/j.jcpa.2009.10.007pubmed: 19897209google scholar: lookup
  47. 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
  48. DeNotta S, McFarlane D. Immunosenescence and Inflammaging in the Aged Horse. Immun. Ageing. 2023;20:2.
    doi: 10.1186/s12979-022-00325-5pmc: PMC9817422pubmed: 36609345google scholar: lookup
  49. Perkins GA, Wagner B. The Development of Equine Immunity: Current Knowledge on Immunology in the Young Horse. Equine Vet. J. 2015;47:267–274.
    doi: 10.1111/evj.12387pubmed: 25405920google scholar: lookup
  50. Hoffman KW, Lee JJ, Foster GA, Krysztof D, Stramer SL, Lim JK. Sex Differences in Cytokine Production Following West Nile Virus Infection: Implications for Symptom Manifestation. Pathog. Dis. 2019;77:ftz016.
    doi: 10.1093/femspd/ftz016pmc: PMC6465207pubmed: 30915442google scholar: lookup
  51. Brien JD, Uhrlaub JL, Nikolich-Žugich J. Protective Capacity and Epitope Specificity of CD8+ T Cells Responding to Lethal West Nile Virus Infection. Eur. J. Immunol. 2007;37:1855–1863.
    doi: 10.1002/eji.200737196pubmed: 17559175google scholar: lookup
  52. Lanteri MC, O’Brien KM, Purtha WE, Cameron MJ, Lund JM, Owen RE, Heitman JW, Custer B, Hirschkorn DF, Tobler LH. Tregs Control the Development of Symptomatic West Nile Virus Infection in Humans and Mice. J. Clin. Investig. 2009;119:3266–3277.
    doi: 10.1172/JCI39387pmc: PMC2769173pubmed: 19855131google scholar: lookup
  53. McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I Interferons in Infectious Disease. Nat. Rev. Immunol. 2015;15:87–103.
    doi: 10.1038/nri3787pmc: PMC7162685pubmed: 25614319google scholar: lookup
  54. Bertram F-M, Thompson PN, Venter M. Epidemiology and Clinical Presentation of West Nile Virus Infection in Horses in South Africa, 2016–2017. Pathogens 2020;10:20.
    doi: 10.3390/pathogens10010020pmc: PMC7823741pubmed: 33396935google scholar: lookup
  55. Peng B-H, Wang T. West Nile Virus Induced Cell Death in the Central Nervous System. Pathogens 2019;8:215.
    doi: 10.3390/pathogens8040215pmc: PMC6963722pubmed: 31683807google scholar: lookup
  56. Marshall EM, Bauer L, Nelemans T, Sooksawasdi Na Ayudhya S, Benavides F, Lanko K, de Vrij FMS, Kushner SA, Koopmans M, van Riel D. Differential Susceptibility of Human Motor Neurons to Infection with Usutu and West Nile Virus. J. Neuroinflamm. 2024;21:236.
    doi: 10.1186/s12974-024-03228-ypmc: PMC11437828pubmed: 39334427google scholar: lookup
  57. Fortuna PRJ, Bielefeldt-Ohmann H, Ovchinnikov DA, Wolvetang EJ, Whitworth DJ. Cortical Neurons Derived from Equine Induced Pluripotent Stem Cells Are Susceptible to Neurotropic Flavivirus Infection and Replication: An In Vitro Model for Equine Neuropathic Diseases. Stem Cells Dev. 2018;27:704–715.
    doi: 10.1089/scd.2017.0106pubmed: 29562867google scholar: lookup
  58. Toplu N, Oğuzoğlu TÇ, Ural K, Albayrak H, Ozan E, Ertürk A, Epikmen ET. West Nile Virus Infection in Horses: Detection by Immunohistochemistry, In Situ Hybridization, and ELISA. Vet. Pathol. 2015;52:1073–1076.
    doi: 10.1177/0300985815570067pubmed: 25677341google scholar: lookup
  59. Roberts JA, Kim CY, Dean A, Kulas KE, St. George K, Hoang HE, Thakur KT. Clinical and Diagnostic Features of West Nile Virus Neuroinvasive Disease in New York City. Pathogens 2024;13:382.
    doi: 10.3390/pathogens13050382pmc: PMC11123700pubmed: 38787234google scholar: lookup
  60. Moreno-Reina C, Martínez-Moya M, Piñero-González de la Peña P, Caro-Domínguez P. Neuroinvasive Disease Due to West Nile Virus: Clinical and Imaging Findings Associated with a Re-Emerging Pathogen. Radiologia 2022;64:473–483.
    doi: 10.1016/j.rx.2021.06.003pubmed: 36243447google scholar: lookup
  61. Lenka A, Kamat A, Mittal SO. Spectrum of Movement Disorders in Patients with Neuroinvasive West Nile Virus Infection. Mov. Disord. Clin. Pract. 2019;6:426–433.
    doi: 10.1002/mdc3.12806pmc: PMC6660229pubmed: 31392241google scholar: lookup
  62. Fratkin JD, Leis AA, Stokic DS, Slavinski SA, Geiss RW. Spinal Cord Neuropathology in Human West NileVirus Infection. Arch. Pathol. Lab. Med. 2004;128:533–537.
    doi: 10.5858/2004-128-533-SCNIHWpubmed: 15086282google scholar: lookup
  63. Blackhurst BM, Funk KE. Molecular and Cellular Mechanisms Underlying Neurologic Manifestations of Mosquito-Borne Flavivirus Infections. Viruses 2023;15:2200.
    doi: 10.3390/v15112200pmc: PMC10674799pubmed: 38005878google scholar: lookup
  64. Mishra N, Boudewijns R, Schmid MA, Marques RE, Sharma S, Neyts J, Dallmeier K. A Chimeric Japanese Encephalitis Vaccine Protects against Lethal Yellow Fever Virus Infection without Inducing Neutralizing Antibodies. mBio 2020;11:e02494-19.
    doi: 10.1128/mBio.02494-19pmc: PMC7157777pubmed: 32265332google scholar: lookup
  65. Yauch LE, Zellweger RM, Kotturi MF, Qutubuddin A, Sidney J, Peters B, Prestwood TR, Sette A, Shresta S. A Protective Role for Dengue Virus-Specific CD8+ T Cells. J. Immunol. 2009;182:4865–4873.
    doi: 10.4049/jimmunol.0801974pmc: PMC2674070pubmed: 19342665google scholar: lookup
  66. Jain N, Oswal N, Chawla AS, Agrawal T, Biswas M, Vrati S, Rath S, George A, Bal V, Medigeshi GR. CD8 T Cells Protect Adult Naive Mice from JEV-Induced Morbidity via Lytic Function. PLoS Neglected Trop. Dis. 2017;11:e0005329.
    doi: 10.1371/journal.pntd.0005329pmc: PMC5308832pubmed: 28151989google scholar: lookup
  67. Tesh RB, Travassos Da Rosa APA, Guzman H, Araujo TP, Xiao S-Y. Immunization with Heterologous Flaviviruses Protective Against Fatal West Nile Encephalitis. Emerg. Infect. Dis. 2002;8:245–251.
    doi: 10.3201/eid0803.010238pmc: PMC2732478pubmed: 11927020google scholar: lookup
  68. Roehrig JT, Staudinger LA, Hunt AR, Mathews JH, Blair CD. Antibody Prophylaxis and Therapy for Flavivirus Encephalitis Infections. Ann. N. Y. Acad. Sci. 2001;951:286–297.
    doi: 10.1111/j.1749-6632.2001.tb02704.xpubmed: 11797785google scholar: lookup
  69. Giordano D, Draves KE, Young LB, Roe K, Bryan MA, Dresch C, Richner JM, Diamond MS, Gale M, Clark EA. Protection of Mice Deficient in Mature B Cells from West Nile Virus Infection by Passive and Active Immunization. PLoS Pathog. 2017;13:e1006743.
    doi: 10.1371/journal.ppat.1006743pmc: PMC5720816pubmed: 29176765google scholar: lookup
  70. Kreil TR, Maier E, Fraiss S, Eibl MM. Neutralizing Antibodies Protect against Lethal Flavivirus Challenge but Allow for the Development of Active Humoral Immunity to a Nonstructural Virus Protein. J. Virol. 1998;72:3076–3081.
    doi: 10.1128/JVI.72.4.3076-3081.1998pmc: PMC109757pubmed: 9525632google scholar: lookup
  71. Chan KR, Ismail AA, Thergarajan G, Raju CS, Yam HC, Rishya M, Sekaran SD. Serological Cross-Reactivity among Common Flaviviruses. Front. Cell Infect. Microbiol. 2022;12:975398.
    doi: 10.3389/fcimb.2022.975398pmc: PMC9519894pubmed: 36189346google scholar: lookup
  72. Hirota J, Nishi H, Matsuda H, Tsunemitsu H, Shimiz S. Cross-Reactivity of Japanese Encephalitis Virus-Vaccinated Horse Sera in Serodiagnosis of West Nile Virus. J. Vet. Med. Sci. 2010;72:369–372.
    doi: 10.1292/jvms.09-0311pubmed: 19996564google scholar: lookup
  73. Endale A, Medhin G, Darfiro K, Kebede N, Legesse M. Magnitude of Antibody Cross-Reactivity in Medically Important Mosquito-Borne Flaviviruses: A Systematic Review. Infect. Drug Resist. 2021;14:4291–4299.
    doi: 10.2147/IDR.S336351pmc: PMC8541746pubmed: 34703255google scholar: lookup
  74. Rathore APS, St. John AL. Cross-Reactive Immunity Among Flaviviruses. Front. Immunol. 2020;11:334.
    doi: 10.3389/fimmu.2020.00334pmc: PMC7054434pubmed: 32174923google scholar: lookup
  75. Watts DM, Tesh RB, Siirin M, da Rosa AT, Newman PC, Clements DE, Ogata S, Coller B-A, Weeks-Levy C, Lieberman MM. Efficacy and Durability of a Recombinant Subunit West Nile Vaccine Candidate in Protecting Hamsters from West Nile Encephalitis. Vaccine 2007;25:2913–2918.
    doi: 10.1016/j.vaccine.2006.08.008pmc: PMC1876746pubmed: 17067727google scholar: lookup
  76. Bosco-Lauth AM, Kooi K, Hawks SA, Duggal NK. Cross-Protection between West Nile Virus and Emerging Flaviviruses in Wild Birds. Am. J. Trop. Med. Hyg. 2024;112:657–662.
    doi: 10.4269/ajtmh.24-0363pmc: PMC11884272pubmed: 39742522google scholar: lookup
  77. Swain SL, McKinstry KK, Strutt TM. Expanding Roles for CD4+ T Cells in Immunity to Viruses. Nat. Rev. Immunol. 2012;12:136–148.
    doi: 10.1038/nri3152pmc: PMC3764486pubmed: 22266691google scholar: lookup
  78. Kalimuddin S, Tham CYL, Chan YFZ, Hang SK, Kunasegaran K, Chia A, Chan CYY, Ng DHL, Sim JXY, Tan H-C. Vaccine-Induced T Cell Responses Control Orthoflavivirus Challenge Infection without Neutralizing Antibodies in Humans. Nat. Microbiol. 2025;10:374–387.
    doi: 10.1038/s41564-024-01903-7pmc: PMC11790491pubmed: 39794472google scholar: lookup
  79. Vargas LAS, Mathew A, Rothman AL. T Lymphocyte Responses to Flaviviruses—Diverse Cell Populations Affect Tendency toward Protection and Disease. Curr. Opin. Virol. 2020;43:28–34.
    doi: 10.1016/j.coviro.2020.07.008pmc: PMC7655706pubmed: 32810785google scholar: lookup
  80. Marzan-Rivera N, Serrano-Collazo C, Cruz L, Pantoja P, Ortiz-Rosa A, Arana T, Martinez MI, Burgos AG, Roman C, Mendez LB. Infection Order Outweighs the Role of CD4+ T Cells in Tertiary Flavivirus Exposure. iScience 2022;25:104764.
    doi: 10.1016/j.isci.2022.104764pmc: PMC9379573pubmed: 35982798google scholar: lookup
  81. Raabe V, Natrajan M.S, Huerta C, Xu Y, Lai L, Mulligan M.J. Immunological Cross-Reactivity to Dengue Virus among Persons with Neuroinvasive West Nile Virus Infection. medRxiv 2022.
    doi: 10.1101/2022.01.03.22268686google scholar: lookup
  82. Percivalle E, Cassaniti I, Sarasini A, Rovida F, Adzasehoun K.M.G, Colombini I, Isernia P, Cuppari I, Baldanti F. West Nile or Usutu Virus? A Three-Year Follow-Up of Humoral and Cellular Response in a Group of Asymptomatic Blood Donors. Viruses 2020;12:157.
    doi: 10.3390/v12020157pmc: PMC7077259pubmed: 32013152google scholar: lookup
  83. Bauswein M, Eid E, Eidenschink L, Schmidt B, Gessner A, Tappe D, Cadar D, Böhmer M.M, Jockel L, van Wickeren N. Detection of Virus-Specific T Cells via ELISpot Corroborates Early Diagnosis in Human Borna Disease Virus 1 (BoDV-1) Encephalitis. Infection 2024;52:1663–1670.
    doi: 10.1007/s15010-024-02246-5pmc: PMC11499394pubmed: 38607591google scholar: lookup
  84. Zhang X, Zhang Y, Jia R, Wang M, Yin Z, Cheng A. Structure and Function of Capsid Protein in Flavivirus Infection and Its Applications in the Development of Vaccines and Therapeutics. Vet. Res. 2021;52:98.
    doi: 10.1186/s13567-021-00966-2pmc: PMC8247181pubmed: 34193256google scholar: lookup
  85. Bunning M.L, Bowen R.A, Cropp B.C, Sullivan K.G, Davis B.S, Komar N, Godsey M, Baker D, Hettler D.L, Holmes D.A. Experimental Infection of Horses with West Nile Virus. Emerg. Infect. Dis. 2002;8:380–386.
    doi: 10.3201/eid0804.010239pmc: PMC3393377pubmed: 11971771google scholar: lookup
  86. Genus: Orthoflavivirus|ICTV. [(accessed on 26 November 2024)]. Available online: https://ictv.global/report/chapter/flaviviridae/flaviviridae/orthoflavivirus.
  87. van den Elsen K, Quek J.P, Luo D. Molecular Insights into the Flavivirus Replication Complex. Viruses 2021;13:956.
    doi: 10.3390/v13060956pmc: PMC8224304pubmed: 34064113google scholar: lookup
  88. Rothan H.A, Kumar M. Role of Endoplasmic Reticulum-Associated Proteins in Flavivirus Replication and Assembly Complexes. Pathogens 2019;8:148.
    doi: 10.3390/pathogens8030148pmc: PMC6789530pubmed: 31547236google scholar: lookup
  89. van den Elsen K, Alvin C.B.L, Sheng H.J, Dahai L. Flavivirus Nonstructural Proteins and Replication Complexes as Antiviral Drug Targets. Curr. Opin. Virol. 2023;59:101305.
    doi: 10.1016/j.coviro.2023.101305pmc: PMC10023477pubmed: 36870091google scholar: lookup
  90. Rastogi M, Sharma N, Singh S.K. Flavivirus NS1: A Multifaceted Enigmatic Viral Protein. Virol. J. 2016;13:131.
    doi: 10.1186/s12985-016-0590-7pmc: PMC4966872pubmed: 27473856google scholar: lookup
  91. Sánchez M.D, Pierson T.C, DeGrace M.M, Mattei L.M, Hanna S.L, Del Piero F, Doms R.W. The Neutralizing Antibody Response against West Nile Virus in Naturally Infected Horses. Virology 2007;359:336–348.
    doi: 10.1016/j.virol.2006.08.047pubmed: 17055550google scholar: lookup
  92. Larsen M.V, Lelic A, Parsons R, Nielsen M, Hoof I, Lamberth K, Loeb M.B, Buus S, Bramson J, Lund O. Identification of CD8+ T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL. PLoS ONE 2010;5:e12697.
    doi: 10.1371/journal.pone.0012697pmc: PMC2939062pubmed: 20856867google scholar: lookup
  93. Kaabinejadian S, Piazza P.A, McMurtrey C.P, Vernon S.R, Cate S.J, Bardet W, Schafer F.B, Jackson K.W, Campbell D.M, Buchli R. Identification of Class I HLA T Cell Control Epitopes for West Nile Virus. PLoS ONE 2013;8:e66298.
    doi: 10.1371/journal.pone.0066298pmc: PMC3677933pubmed: 23762485google scholar: lookup
  94. Waller F.M, Reche P.A, Flower D.R. West Nile Virus Vaccine Design by T Cell Epitope Selection: In Silico Analysis of Conservation, Functional Cross-Reactivity with the Human Genome, and Population Coverage. J. Immunol. Res. 2020;2020:7235742.
    doi: 10.1155/2020/7235742pmc: PMC7106935pubmed: 32258174google scholar: lookup
  95. McMurtrey C.P, Lelic A, Piazza P, Chakrabarti A.K, Yablonsky E.J, Wahl A, Bardet W, Eckerd A, Cook R.L, Hess R. Epitope Discovery in West Nile Virus Infection: Identification and Immune Recognition of Viral Epitopes. Proc. Natl. Acad. Sci. USA 2008;105:2981–2986.
    doi: 10.1073/pnas.0711874105pmc: PMC2268571pubmed: 18299564google scholar: lookup
  96. Sharma P, Sharma P, Mishra S, Kumar A. Analysis of Promiscuous T Cell Epitopes for Vaccine Development Against West Nile Virus Using Bioinformatics Approaches. Int. J. Pept. Res. Ther. 2018;24:377–387.
    doi: 10.1007/s10989-017-9624-2google scholar: lookup
  97. Koblischke M, Spitzer F.S, Florian D.M, Aberle S.W, Malafa S, Fae I, Cassaniti I, Jungbauer C, Knapp B, Laferl H. CD4 T Cell Determinants in West Nile Virus Disease and Asymptomatic Infection. Front. Immunol. 2020;11:16.
    doi: 10.3389/fimmu.2020.00016pmc: PMC6989424pubmed: 32038660google scholar: lookup
  98. Koblischke M, Stiasny K, Aberle S.W, Malafa S, Tsouchnikas G, Schwaiger J, Kundi M, Heinz F.X, Aberle J.H. Structural Influence on the Dominance of Virus-Specific CD4 T Cell Epitopes in Zika Virus Infection. Front. Immunol. 2018;9:1196.
    doi: 10.3389/fimmu.2018.01196pmc: PMC5989350pubmed: 29899743google scholar: lookup
  99. Tick-Borne Encephalitis Virus: A Quest for Better Vaccines Against a Virus on the Rise. [(accessed on 24 June 2025)]. Available online: https://www.mdpi.com/2076-393X/8/3/451.
  100. De Filette M, Chabierski S, Andries O, Ulbert S, Sanders N.N. T Cell Epitope Mapping of the E-Protein of West Nile Virus in BALB/c Mice. PLoS ONE 2014;9:e115343.
    doi: 10.1371/journal.pone.0115343pmc: PMC4266646pubmed: 25506689google scholar: lookup
  101. Brien J.D, Uhrlaub J.L, Nikolich-Zugich J. West Nile Virus-Specific CD4 T Cells Exhibit Direct Antiviral Cytokine Secretion and Cytotoxicity and Are Sufficient for Antiviral Protection. J. Immunol. 2008;181:8568–8575.
    doi: 10.4049/jimmunol.181.12.8568pmc: PMC3504655pubmed: 19050276google scholar: lookup
  102. Körber N, Behrends U, Protzer U, Bauer T. Evaluation of T-Activated Proteins as Recall Antigens to Monitor Epstein–Barr Virus and Human Cytomegalovirus-Specific T Cells in a Clinical Trial Setting. J. Transl. Med. 2020;18:242.
    doi: 10.1186/s12967-020-02385-xpmc: PMC7298696pubmed: 32552697google scholar: lookup
  103. Kreutzfeldt N, Chambers T.M, Reedy S, Spann K.M, 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. 2023;38:424–430.
    doi: 10.1111/jvim.16978pmc: PMC10800231pubmed: 38141173google scholar: lookup
  104. Witkowska-Piłaszewicz O, Pingwara R, Szczepaniak J, Winnicka A. The Effect of the Clenbuterol—Β2-Adrenergic Receptor Agonist on the Peripheral Blood Mononuclear Cells Proliferation, Phenotype, Functions, and Reactive Oxygen Species Production in Race Horses In Vitro. Cells 2021;10:936.
    doi: 10.3390/cells10040936pmc: PMC8072563pubmed: 33920705google scholar: lookup
  105. Dąbrowska I, Grzędzicka J, Niedzielska A, Witkowska-Piłaszewicz O. Impact of Chlorogenic Acid on Peripheral Blood Mononuclear Cell Proliferation, Oxidative Stress, and Inflammatory Responses in Racehorses during Exercise. Antioxidants 2023;12:1924.
    doi: 10.3390/antiox12111924pmc: PMC10669817pubmed: 38001777google scholar: lookup
  106. Couëtil L.L, Cardwell J.M, Gerber V, Lavoie J.-P, Léguillette R, Richard E.A. Inflammatory Airway Disease of Horses—Revised Consensus Statement. J. Vet. Intern. Med. 2016;30:503–515.
    doi: 10.1111/jvim.13824pmc: PMC4913592pubmed: 26806374google scholar: lookup
  107. Couetil L, Cardwell J.M, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie J.-P. Equine Asthma: Current Understanding and Future Directions. Front. Vet. Sci. 2020;7:450.
    doi: 10.3389/fvets.2020.00450pmc: PMC7438831pubmed: 32903600google scholar: lookup
  108. Ni D, Tan J, Niewold P, Spiteri A.G, Pinget G.V, Stanley D, King N.J.C, Macia L. Impact of Dietary Fiber on West Nile Virus Infection. Front. Immunol. 2022;13:784486.
    doi: 10.3389/fimmu.2022.784486pmc: PMC8919037pubmed: 35296081google scholar: lookup
  109. Lin S.-C, Zhao F.R, Janova H, Gervais A, Rucknagel S, Murray K.O, Casanova J.-L, Diamond M.S. Blockade of Interferon Signaling Decreases Gut Barrier Integrity and Promotes Severe West Nile Virus Disease. Nat. Commun. 2023;14:5973.
    doi: 10.1038/s41467-023-41600-3pmc: PMC10520062pubmed: 37749080google scholar: lookup
  110. [(accessed on 7 August 2025)]. Available online: https://www.ecdc.europa.eu/en/news-events/epidemiological-update-west-nile-virus-transmission-season-europe-2023-0.
  111. Jameson S.C, Masopust D. Understanding Subset Diversity in T Cell Memory. Immunity 2018;48:214–226.
    doi: 10.1016/j.immuni.2018.02.010pmc: PMC5863745pubmed: 29466754google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,002 horse owners like you who receive our email updates on horse health and nutrition.