Analyze Diet
Equine veterinary journal2026; doi: 10.1002/evj.70191

CXCL16-associated genetic susceptibility to equine viral arteritis in export-bound horses from Spain.

Abstract: Equine viral arteritis (EVA) remains a relevant health and economic concern due to the ability of some infected stallions to establish long-term persistent infection with equine arteritis virus (EAV). Allelic variation in the CXCL16 gene has been identified as a determinant of susceptibility or resistance to the carrier state, positioning genotyping as a useful tool for risk-based reproductive and health management. Objective: To characterise the distribution of CXCL16 genotypes in export-bound horses from Spain and to assess the utility of CXCL16 genotyping for EVA prevention and control. Methods: Cross-sectional observational study. Methods: A total of 1004 horses of multiple breeds and geographic origins were included. CXCL16 genotypes were determined in all animals, and EAV serological status was assessed in a subset of 358 samples using ELISA. Genotypic frequencies were calculated, and associations with breed and sex were analysed. Results: The resistant genotype (CXCL16) predominated in the study population (57.3%), although marked breed-related variability was observed. Lower frequencies of the resistant genotype were detected in Iberian breeds, including Spanish Purebred (53.3%) and Lusitano (38.3%), with higher frequencies observed in Thoroughbreds (77.6%) and European sport horse breeds. Breed composition was the main factor associated with differences in CXCL16-associated susceptibility profiles, while the effect of sex was limited. Among the 358 horses tested by ELISA, 3.9% (n = 14) were seropositive for EAV. Conclusions: The study population was restricted to export-bound horses; some breeds were underrepresented, and the cross-sectional design did not allow direct assessment of long-term viral persistence. Conclusions: This is the first large-scale characterisation of CXCL16 genotype distribution in export-bound horses in Spain and demonstrates marked breed-related differences in genetic susceptibility to EAV persistence. CXCL16 genotyping represents a valuable complementary tool to serological surveillance for supporting risk-based EVA management and informed decision-making in breeding and export programmes.
Publication Date: 2026-05-14 PubMed ID: 42135260DOI: 10.1002/evj.70191Google 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.
  • 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 article investigates how genetic variations in the CXCL16 gene influence the susceptibility of export-bound horses from Spain to equine viral arteritis (EVA), a viral disease affecting horses.
  • The study evaluates the distribution of CXCL16 genotypes across different horse breeds and discusses the potential of CXCL16 genotyping to improve EVA prevention and control strategies in horse breeding and export programs.

Background and Importance

  • Equine viral arteritis (EVA) is a disease caused by the equine arteritis virus (EAV), which can have significant health and economic impacts within the horse industry.
  • One major concern is that some stallions infected with EAV can become long-term persistent carriers, contributing to the spread of the virus.
  • Previous research has identified that allelic variation in the CXCL16 gene is a key factor determining whether a horse is susceptible or resistant to becoming a carrier of EAV.
  • Thus, identifying the CXCL16 genotype can help in managing risk by informing strategies that prevent the establishment of persistent EAV infection.

Study Objectives

  • Characterize the distribution of CXCL16 genotypes in a large population of export-bound horses from Spain.
  • Assess the potential utility of CXCL16 genotyping as a tool to inform EVA prevention and control measures.

Methods

  • Design: Cross-sectional observational study involving 1004 horses of various breeds and geographic origins bound for export.
  • Genotyping: All horses were genotyped for CXCL16 allelic variants related to EVA susceptibility or resistance.
  • Serology: A subset of 358 horses was tested for the presence of antibodies against EAV using ELISA to determine previous exposure or infection status.
  • Data Analysis: The study calculated the frequency of CXCL16 genotypes overall and by breed, as well as investigated associations between genotype frequency and factors such as breed and sex.

Key Results

  • The resistant CXCL16 genotype was the most frequent in the overall studied population (57.3%), indicating a majority with genetic resistance to EAV persistence.
  • However, considerable variability in genotype distribution was observed between breeds:
    • Iberian breeds such as the Spanish Purebred (53.3%) and Lusitano (38.3%) had lower frequencies of the resistant genotype.
    • In contrast, Thoroughbreds (77.6%) and European sport horse breeds showed higher frequencies of the resistant genotype.
  • Breed composition was strongly associated with differences in CXCL16 susceptibility profiles.
  • The effect of sex on genotype distribution was minimal.
  • Among the subset tested serologically, 3.9% (14 horses) were seropositive for EAV, showing a low level of prior viral exposure or infection.

Conclusions and Implications

  • This study is the first large-scale examination of CXCL16 genotype distribution in export-bound horses in Spain, highlighting notable breed-related genetic differences in susceptibility to EAV persistence.
  • The breed-related variability suggests that certain breeds may be at higher risk of becoming carriers and hence may require tailored risk management strategies.
  • Because the study was cross-sectional and export-bound, it could not directly assess long-term viral persistence or fully represent other horse populations and breeds.
  • CXCL16 genotyping emerges as a valuable complementary tool to serological testing, providing genetic information that supports more informed decision-making in breeding, reproductive management, and export programs.
  • Incorporating CXCL16 genotyping could:
    • Enhance risk-based EVA surveillance programs.
    • Help identify horses less likely to become carriers before breeding or export.
    • Reduce transmission risks and economic losses associated with EVA.

Cite This Article

APA
Gago P, Cruz-Lopez F, Dorrego A, Rivera B, de Juan L, Lorente-Leal V. (2026). CXCL16-associated genetic susceptibility to equine viral arteritis in export-bound horses from Spain. Equine Vet J. https://doi.org/10.1002/evj.70191

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Gago, Paloma
  • VISAVET Health Surveillance Centre, Universidad Complutense Madrid, Madrid, Spain.
  • Animal Health Department, Faculty of Veterinary Medicine, Universidad Complutense Madrid, Madrid, Spain.
Cruz-Lopez, Fatima
  • VISAVET Health Surveillance Centre, Universidad Complutense Madrid, Madrid, Spain.
Dorrego, Abel
  • VISAVET Health Surveillance Centre, Universidad Complutense Madrid, Madrid, Spain.
Rivera, Belen
  • VISAVET Health Surveillance Centre, Universidad Complutense Madrid, Madrid, Spain.
de Juan, Lucia
  • VISAVET Health Surveillance Centre, Universidad Complutense Madrid, Madrid, Spain.
  • Animal Health Department, Faculty of Veterinary Medicine, Universidad Complutense Madrid, Madrid, Spain.
Lorente-Leal, Víctor
  • VISAVET Health Surveillance Centre, Universidad Complutense Madrid, Madrid, Spain.
  • Genetics, Physiology and Microbiology Department, Faculty of Biological Sciences, Universidad Complutense Madrid, Madrid, Spain.

Grant Funding

  • CT82/20-CT83/20 / Universidad Complutense de Madrid - Banco Santander
  • Grants for Predoctoral Researchers Training Contracts

References

This article includes 56 references
  1. Balasuriya UBR, Go YY, MacLachlan NJ. Equine arteritis virus. Vet Microbiol 2013;167(1):93–122.
  2. Paweska JT, Aitchison H, Chirnside ED, Barnard BJ. Transmission of the south African asinine strain of equine arteritis virus (EAV) among horses and between donkeys and horses. Onderstepoort J Vet Res 1996;63(3):189–196.
  3. Timoney PJ. Factors influencing the international spread of equine diseases. Vet Clin North Am Equine Pract 2000;16(3):537–551.
  4. Timoney PJ, McCollum WH. Equine viral arteritis: epidemiology and control. J Equine Vet Sci 1988;8(1):54–59.
  5. Balasuriya UBR, Carossino M, Timoney PJ. Equine viral arteritis: a respiratory and reproductive disease of significant economic importance to the equine industry. Equine Vet Educ 2018;30(9):497–512.
    doi: 10.1111/eve.12672google scholar: lookup
  6. Timoney PJ, McCollum WH. Equine viral arteritis. Vet Clin North Am Equine Pract 1993;9(2):295–309.
  7. Cavanagh D. Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 1997;142(3):629–633.
  8. Brinton MA, Gulyaeva AA, Balasuriya UBR, Dunowska M, Faaberg KS, Goldberg T. ICTV virus taxonomy profile: Arteriviridae 2021. J Gen Virol 2021;102(8):001632.
    doi: 10.1099/jgv.0.001632google scholar: lookup
  9. Kuhn JH, Lauck M, Bailey AL, Shchetinin AM, Vishnevskaya TV, Bào Y. Reorganization and expansion of the nidoviral family Arteriviridae. Arch Virol 2016;161(3):755–768.
    doi: 10.1007/s00705-015-2672-zgoogle scholar: lookup
  10. Glaser AL, de Vries AA, Rottier PJ, Horzinek MC, Colenbrander B. Equine arteritis virus: a review of clinical features and management aspects. Vet Q 1996;18(3):95–99.
  11. McFadden AMJ, Pearce PV, Orr D, Nicoll K, Rawdon TG, Pharo H. Evidence for absence of equine arteritis virus in the horse population of New Zealand. N Z Vet J 2013;61(5):300–304.
  12. Cole JR, Hall RF, Gosser HS, Hendricks JB, Pursell AR, Senne DA. Transmissibility and abortogenic effect of equine viral arteritis in mares. J Am Vet Med Assoc 1986;189(7):769–771.
  13. Guthrie AJ, Howell PG, Hedges JF, Bosman AM, Balasuriya UBR, McCollum WH. Lateral transmission of equine arteritis virus among Lipizzaner stallions in South Africa. Equine Vet J 2003;35(6):596–600.
  14. Holyoak GR, Balasuriya UBR, Broaddus CC, Timoney PJ. Equine viral arteritis: current status and prevention. Theriogenology 2008;70(3):403–414.
  15. Balasuriya UBR. Equine Viral Arteritis. New Perspect Infect Dis 2014;30(3):543–560.
  16. Balasuriya UBR, Snijder EJ, Van Dinten LC, Heidner HW, Wilson WD, Hedges JF. Equine arteritis virus derived from an infectious cDNA clone is attenuated and genetically stable in infected stallions.. Virology 1999;260(1):201–208.
    doi: 10.1006/viro.1999.9817google scholar: lookup
  17. Balasuriya UBR, Snijder EJ, Heidner HW, Zhang J, Zevenhoven‐Dobbe JC, Boone JD. Development and characterization of an infectious cDNA clone of the virulent Bucyrus strain of equine arteritis virus.. J Gen Virol 2007;88(Pt 3):918–924.
    doi: 10.1099/vir.0.82415-0google scholar: lookup
  18. MacLachlan NJ, Balasuriya UB, Rossitto PV, Hullinger PA, Patton JF, Wilson WD. Fatal experimental equine arteritis virus infection of a pregnant mare: immunohistochemical staining of viral antigens.. J Vet Diagn Invest 1996;8(3):367–374.
  19. McCollum WH, Timoney PJ, Tengelsen LA. Clinical, virological and serological responses of donkeys to intranasal inoculation with the KY‐84 strain of equine arteritis virus.. J Comp Pathol 1995;112(2):207–211.
  20. Vairo S, Vandekerckhove A, Steukers L, Glorieux S, Van den Broeck W, Nauwynck H. Clinical and virological outcome of an infection with the Belgian equine arteritis virus strain 08P178.. Vet Microbiol 2012;157(3):333–344.
  21. Bażanów BA, Frącka AB, Jackulak NA, Staroniewicz ZM, Ploch SM. A 34‐year retrospective study of equine viral abortion in Poland.. Pol J Vet Sci 2014;17(4):607–612.
    doi: 10.2478/pjvs-2014-0091google scholar: lookup
  22. Del Piero F, Wilkins PA, Lopez JW, Glaser AL, Dubovi EJ, Schlafer DH. Equine viral arteritis in newborn foals: clinical, pathological, serological, microbiological and immunohistochemical observations.. Equine Vet J 1997;29(3):178–185.
  23. Vaala WE, Hamir AN, Dubovi EJ, Timoney PJ, Ruiz B. Fatal, congenitally acquired infection with equine arteritis virus in a neonatal thoroughbred.. Equine Vet J 1992;24(2):155–158.
  24. Balasuriya UBR, Sarkar S, Carossino M, Go YY, Chelvarajan L, Cook RF. Host factors that contribute to equine arteritis virus persistence in the stallion: an update.. J Equine Vet Sci 2016;43:S11–S17.
  25. Campos JR, Breheny P, Araujo RR, Troedsson MHT, Squires EL, Timoney PJ. Semen quality of stallions challenged with the Kentucky 84 strain of equine arteritis virus.. Theriogenology 2014;82(8):1068–1079.
  26. McCollum WH, Little TV, Timoney PJ, Swerczek TW. Resistance of castrated male horses to attempted establishment of the carrier state with equine arteritis virus.. J Comp Pathol 1994;111(4):383–388.
  27. Balasuriya UB, Carossino M. Reproductive effects of arteriviruses: equine arteritis virus and porcine reproductive and respiratory syndrome virus infections.. Curr Opin Virol 2017;27:57–70.
  28. Holyoak GR, Little TV, McCollum WH, Timoney PJ. Relationship between onset of puberty and establishment of persistent infection with equine arteritis virus in the experimentally infected colt.. J Comp Pathol 1993;109(1):29–46.
  29. Timoney PJ, McCollum WH, Murphy TW, Roberts AW, Willard JG, Carswell GD. The carrier state in equine arteritis virus infection in the stallion with specific emphasis on the venereal mode of virus transmission.. J Reprod Fertil Suppl 1987;35:95–102.
  30. Go YY, Zhang J, Timoney PJ, Cook RF, Horohov DW, Balasuriya UBR. Complex interactions between the major and minor envelope proteins of equine arteritis virus determine its tropism for equine CD3+ T lymphocytes and CD14+ monocytes.. J Virol 2010;84(10):4898–4911.
    doi: 10.1128/jvi.02743-09google scholar: lookup
  31. Go YY, Cook RF, Fulgêncio JQ, Campos JR, Henney P, Timoney PJ. Assessment of correlation between in vitro CD3+ T cell susceptibility to EAV infection and clinical outcome following experimental infection. Vet Microbiol 2012;157(1):220–225.
  32. Young Go Y, Bailey EG, Cook D. Genome‐wide association study among four horse breeds identifies a common haplotype associated with in vitro CD3+ T cell susceptibility/resistance to equine arteritis virus infection. J Virol 2011;85(24):13174–13184.
    doi: 10.1128/jvi.06068-11google scholar: lookup
  33. Sarkar S, Chelvarajan L, Go YY, Cook F, Artiushin S, Mondal S. Equine arteritis virus uses equine CXCL16 as an entry receptor. J Virol 2016;90(7):3366–3384.
    doi: 10.1128/jvi.02455-15google scholar: lookup
  34. Carossino M, Loynachan AT, Canisso IF, Cook RF, Campos JR, Nam B. Equine arteritis virus has specific tropism for stromal cells and CD8+ T and CD21+ B lymphocytes but not for glandular epithelium at the primary site of persistent infection in the stallion reproductive tract. J Virol 2017;91(13):e00418‐17.
    doi: 10.1128/jvi.00418-17google scholar: lookup
  35. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Cook RF. Equine arteritis virus long‐term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis. PLoS Pathog 2019;15(7):e1007950.
  36. Sarkar S, Bailey E, Go YY, Cook RF, Kalbfleisch T, Eberth J. Allelic variation in CXCL16 determines CD3+ T lymphocyte susceptibility to equine arteritis virus infection and establishment of long‐term carrier state in the stallion. PLoS Genet 2016;12(12):e1006467.
  37. Socha W, Larska M, Rola J. Molecular investigation of allelic variants of EqCXCL16 gene in equine arteritis virus infected stallions of selected horse breeds in Poland. Infect Genet Evol 2020;85:104455.
  38. Thieulent CJ, Carossino M, Balasuriya UBR, Graves K, Bailey E, Eberth J. Development of a TaqMan® allelic discrimination qPCR assay for rapid detection of equine CXCL16 allelic variants associated with the establishment of long‐term equine arteritis virus carrier state in stallions. Front Genet 2022;13:871875.
    doi: 10.3389/fgene.2022.871875google scholar: lookup
  39. Cruz F, Fores P, Mughini‐Gras L, Ireland J, Moreno MA, Newton R. Seroprevalence and factors associated with seropositivity to equine arteritis virus in Spanish purebred horses in Spain. Equine Vet J 2016;48(5):573–577.
    doi: 10.1111/evj.12500google scholar: lookup
  40. Legrand L, Pitel PH, Fortier G, Pronost S, Vabret A. Testing for antibodies to equine arteritis virus. Vet Rec 2007;161(17):599–600.
    doi: 10.1136/vr.161.17.599-agoogle scholar: lookup
  41. Cañon J, Checa ML, Carleos C, Vega‐Pla JL, Vallejo M, Dunner S. The genetic structure of Spanish Celtic horse breeds inferred from microsatellite data. Anim Genet 2000;31(1):39–48.
  42. Luís C, Bastos‐Silveira C, Cothran EG, Oom MM. Iberian origins of New World horse breeds. J Hered 2006;97(2):107–113.
    doi: 10.1093/jhered/esj020google scholar: lookup
  43. Royo LJ, Álvarez I, Beja‐Pereira A, Molina A, Fernández I, Jordana J. The origins of Iberian horses assessed via mitochondrial DNA. J Hered 2005;96(6):663–669.
    doi: 10.1093/jhered/esi116google scholar: lookup
  44. Bartolomé E, Cervantes I, Valera M, Gutiérrez JP. Influence of foreign breeds on the genetic structure of the Spanish sport horse population. Livest Sci 2011;142(1):70–79.
  45. Hill EW, Bradley DG, Al‐Barody M, Ertugrul O, Splan RK, Zakharov I. History and integrity of thoroughbred dam lines revealed in equine mtDNA variation. Anim Genet 2002;33(4):287–294.
  46. Cortés O, Dunner S, Gama LT, Martínez AM, Delgado JV, Ginja C. The legacy of Columbus in American horse populations assessed by microsatellite markers.. J Anim Breed Genet 2017;134(4):340–350.
    doi: 10.1111/jbg.12255google scholar: lookup
  47. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Shuck KM. Downregulation of MicroRNA eca‐mir‐128 in seminal exosomes and enhanced expression of CXCL16 in the stallion reproductive tract are associated with long‐term persistence of equine arteritis virus.. J Virol 2018;92(9):e00015‐18.
    doi: 10.1128/jvi.00015-18google scholar: lookup
  48. Socha W, Sztromwasser P, Dunowska M, Jaklinska B, Rola J. Spread of equine arteritis virus among Hucul horses with different EqCXCL16 genotypes and analysis of viral quasispecies from semen of selected stallions.. Sci Rep 2020;10:2909.
  49. Cruz‐Lopez F, Newton R, Sanchez‐Rodriguez A, Ireland J, Mughini‐Gras L, Moreno MA. Equine viral arteritis in breeding and sport horses in central Spain.. Res Vet Sci 2017;115:88–91.
  50. Franco JJ, Gonzálvez M, Cano‐Terriza D, Barbero‐Moyano J, Jose‐Cunilleras E, Alguacil E. Equine viral arteritis: Seroprevalence patterns and risk factors in equids from western Europe.. Res Vet Sci 2025;192:105701.
  51. Camino E, Pozo P, Dorrego A, Carvajal KA, Buendia A, Gonzalez S. Importance of equine piroplasmosis antibody presence in Spanish horses prior to export.. Ticks Tick‐Borne Dis 2020;11(2):101329.
  52. Camino E, Buendia A, Dorrego A, Pozo P, de Juan L, Dominguez L. Sero‐molecular survey and risk factors of equine piroplasmosis in horses in Spain.. Equine Vet J 2021;53(4):771–779.
    doi: 10.1111/evj.13348google scholar: lookup
  53. Newton JR, Wood JLN, Castillo‐Olivares FJ, Mumford JA. Serological surveillance of equine viral arteritis in the United Kingdom since the outbreak in 1993.. Vet Rec 1999;145(18):511–516.
    doi: 10.1136/vr.145.18.511google scholar: lookup
  54. Huntington P, Forman A, Ellis P. The occurrence of equine arteritis virus in Australia.. Aust Vet J 1990;67(12):432–435.
  55. Timoney PJ, McCollum WH. Equine viral arteritis in perspective in relation to international trade.. J Equine Vet Sci 1993;13(1):50–52.
  56. Anon. II Estudio del Impacto del Sector Ecuestre en España [Second study on the impact of the equestrian sector in Spain]. Madrid: Green Oak Group and Deloitte, S.L.; 2022. p. 26 [cited 2026 Jan 15]. Available from: https://www.animalshealth.es/fileuploads/user/PDF/2022/03/Segundo_Estudio_Impacto_Sector_Ecuestre_Espana.pdf

Citations

This article has been cited 0 times.