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Journal of virology2017; 91(13); doi: 10.1128/JVI.00418-17

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.

Abstract: Equine arteritis virus (EAV) has a global impact on the equine industry as the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. A distinctive feature of EAV infection is that it establishes long-term persistent infection in 10 to 70% of infected stallions (carriers). In these stallions, EAV is detectable only in the reproductive tract, and viral persistence occurs despite the presence of high serum neutralizing antibody titers. Carrier stallions constitute the natural reservoir of the virus as they continuously shed EAV in their semen. Although the accessory sex glands have been implicated as the primary sites of EAV persistence, the viral host cell tropism and whether viral replication in carrier stallions occurs in the presence or absence of host inflammatory responses remain unknown. In this study, dual immunohistochemical and immunofluorescence techniques were employed to unequivocally demonstrate that the ampulla is the main EAV tissue reservoir rather than immunologically privileged tissues (i.e., testes). Furthermore, we demonstrate that EAV has specific tropism for stromal cells (fibrocytes and possibly tissue macrophages) and CD8+ T and CD21+ B lymphocytes but not glandular epithelium. Persistent EAV infection is associated with moderate, multifocal lymphoplasmacytic ampullitis comprising clusters of B (CD21+) lymphocytes and significant infiltration of T (CD3+, CD4+, CD8+, and CD25+) lymphocytes, tissue macrophages, and dendritic cells (Iba-1+ and CD83+), with a small number of tissue macrophages expressing CD163 and CD204 scavenger receptors. This study suggests that EAV employs complex immune evasion mechanisms that warrant further investigation.IMPORTANCE The major challenge for the worldwide control of EAV is that this virus has the distinctive ability to establish persistent infection in the stallion's reproductive tract as a mechanism to ensure its maintenance in equid populations. Therefore, the precise identification of tissue and cellular tropism of EAV is critical for understanding the molecular basis of viral persistence and for development of improved prophylactic or treatment strategies. This study significantly enhances our understanding of the EAV carrier state in stallions by unequivocally identifying the ampullae as the primary sites of viral persistence, combined with the fact that persistence involves continuous viral replication in fibrocytes (possibly including tissue macrophages) and T and B lymphocytes in the presence of detectable inflammatory responses, suggesting the involvement of complex viral mechanisms of immune evasion. Therefore, EAV persistence provides a powerful new natural animal model to study RNA virus persistence in the male reproductive tract.
Publication Date: 2017-06-09 PubMed ID: 28424285PubMed Central: PMC5469258DOI: 10.1128/JVI.00418-17Google Scholar: Lookup
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  • 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.

The study discusses how the Equine Arteritis Virus (EAV) uniquely affects specific cells within a stallion’s reproductive tract, establishing persistent infection despite the immune response. It provides critical insight into understanding the EAV’s carrier state in stallions and offers a natural animal model for studying RNA virus persistence in the male reproductive tract.

Research Context

  • This research is based on Equine Arteritis Virus (EAV), a globally recognized disease that affects horses. EAV is the cause of equine viral arteritis (EVA), a disease with respiratory, systemic, and reproductive impacts.
  • EAV manages to establish persistent infections in 10 to 70% of infected stallions, despite existing neutralizing antibody responses in the horses. This ability to persist makes the ‘carrier’ stallions the natural virus reservoir, as they continually shed the virus in their semen.
  • However, the focus of EAV persistence, as well as the specifics of its interaction with different cell types (its “tropism”), was previously unknown, driving the need for this research.

Findings and Implications

  • The researchers used advanced techniques to confirm that the main tissue reservoir of EAV is the ampulla within the stallion’s reproductive tract, rather than the testes which were previously suggested as possible sites.
  • The study found that EAV specifically targets stromal cells (like fibrocytes and possibly tissue macrophages) and two types of lymphocytes (CD8 T and CD21 B cells), but it leaves the glandular epithelium unaffected. This specific targeting is referred to as the virus’s ‘tropism’.
  • Persistent EAV infection was associated with observable inflammation symptoms, defined as ‘ampullitis’, which involved the aggregation of the targeted lymphocytes and infiltration of other immune cells. This could suggest a complex interplay between the virus and the host’s immune response.
  • Understanding EAV’s cellular tropism, persistence mechanisms, and immune system interactions can contribute to better prevention or treatment strategies against EVA.
  • The results also open up a new natural animal model to study RNA virus persistence in the male reproductive tract, which could be of significant use in other virology studies.

Cite This Article

APA
Carossino M, Loynachan AT, Canisso IF, Cook RF, Campos JR, Nam B, Go YY, Squires EL, Troedsson MHT, Swerczek T, Del Piero F, Bailey E, Timoney PJ, Balasuriya UBR. (2017). 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, 91(13). https://doi.org/10.1128/JVI.00418-17

Publication

ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 91
Issue: 13

Researcher Affiliations

Carossino, Mariano
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Loynachan, Alan T
  • University of Kentucky Veterinary Diagnostic Laboratory, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Canisso, Igor F
  • Department of Veterinary Clinical Medicine and Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
Cook, R Frank
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Campos, Juliana R
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Nam, Bora
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Go, Yun Young
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
  • Virus Research and Testing Group, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, South Korea.
Squires, Edward L
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Troedsson, Mats H T
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Swerczek, Thomas
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Del Piero, Fabio
  • Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Bailey, Ernest
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Timoney, Peter J
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Balasuriya, Udeni B R
  • Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA ubalasuriya@uky.edu.

MeSH Terms

  • Animals
  • Arterivirus Infections / veterinary
  • Arterivirus Infections / virology
  • B-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / virology
  • Epithelium / virology
  • Equartevirus / physiology
  • Fluorescent Antibody Technique
  • Genitalia / virology
  • Horse Diseases / virology
  • Horses
  • Immunohistochemistry
  • Male
  • Stromal Cells / virology
  • Viral Tropism

References

This article includes 119 references
  1. Cavanagh D. Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 142:629–633.
    pubmed: 9349308
  2. Balasuriya U, MacLachlan NJ. 2013. Equine viral arteritis, p 169–181. In Sellon DC, Long MT (ed), Equine infectious diseases, 2nd ed Saunders, St. Louis, MO.
  3. Balasuriya UB, Go YY, MacLachlan NJ. Equine arteritis virus. Vet Microbiol 167:93–122.
  4. 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 .
    doi: 10.1111/eve.12672google scholar: lookup
  5. Timoney PJ. The increasing significance of international trade in equids and its influence on the spread of infectious diseases. Ann N Y Acad Sci 916:55–60.
    pubmed: 11193671
  6. Timoney PJ. Factors influencing the international spread of equine diseases. Vet Clin North Am Equine Pract 16:537–551.
    pubmed: 11219348
  7. Timoney PJ, McCollum WH. Equine viral arteritis: epidemiology and control. J Equine Vet Sci 8:54–59.
  8. Timoney PJ, McCollum WH. Equine viral arteritis. Vet Clin North Am Equine Pract 9:295–309.
    pmc: PMC7134676pubmed: 8395325
  9. Snijder EJ, Meulenberg JJ. The molecular biology of arteriviruses. J Gen Virol 79:961–979.
    doi: 10.1099/0022-1317-79-5-961pubmed: 9603311google scholar: lookup
  10. Snijder EJ, Kikkert M, Fang Y. Arterivirus molecular biology and pathogenesis. J Gen Virol 94:2141–2163.
    doi: 10.1099/vir.0.056341-0pubmed: 23939974google scholar: lookup
  11. Lopez JW, del Piero F, Glaser A, Finazzi M. Immunoperoxidase histochemistry as a diagnostic tool for detection of equine arteritis virus antigen in formalin fixed tissues. Equine Vet J 28:77–79.
  12. Del Piero F. Equine viral arteritis. Vet Pathol 37:287–296.
    doi: 10.1354/vp.37-4-287pubmed: 10896389google scholar: lookup
  13. Del Piero F. Diagnosis of equine arteritis virus infection in two horses by using monoclonal antibody immunoperoxidase histochemistry on skin biopsies. Vet Pathol 37:486–487.
    doi: 10.1354/vp.37-5-486pubmed: 11055877google scholar: lookup
  14. Bryans JT, Doll ER, Jones TC. The lesions of equine viral arteritis. Cornell Vet 47:52–68.
    pubmed: 13397179
  15. 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 8:367–374.
    doi: 10.1177/104063879600800316pubmed: 8844583google scholar: lookup
  16. Vairo S, Favoreel H, Scagliarini A, Nauwynck H. Identification of target cells of a European equine arteritis virus strain in experimentally infected ponies. Vet Microbiol 167:235–241.
    doi: 10.1016/j.vetmic.2013.07.020pubmed: 23993255google scholar: lookup
  17. 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 157:333–344.
    doi: 10.1016/j.vetmic.2012.01.014pubmed: 22306037google scholar: lookup
  18. Balasuriya U. Equine viral arteritis. Vet Clin North Am Equine Pract 30:543–560.
    doi: 10.1016/j.cveq.2014.08.011pubmed: 25441113google scholar: lookup
  19. Balasuriya UB, Snijder EJ, Heidner HW, Zhang J, Zevenhoven-Dobbe JC, Boone JD, McCollum WH, Timoney PJ, MacLachlan NJ. Development and characterization of an infectious cDNA clone of the virulent Bucyrus strain of equine arteritis virus. J Gen Virol 88:918–924.
    doi: 10.1099/vir.0.82415-0pubmed: 17325365google scholar: lookup
  20. Balasuriya UB, Snijder EJ, van Dinten LC, Heidner HW, Wilson WD, Hedges JF, Hullinger PJ, MacLachlan NJ. Equine arteritis virus derived from an infectious cDNA clone is attenuated and genetically stable in infected stallions. Virology 260:201–208.
    doi: 10.1006/viro.1999.9817pubmed: 10405372google scholar: lookup
  21. Campos JR. Effects on semen quality and on establishment of persistent equine arteritis virus (EAV) infection in stallions following experimental challenge with the Kentucky 84 (KY84) strain. .
  22. Go YY, Cook RF, Fulgencio JQ, Campos JR, Henney P, Timoney PJ, Horohov DW, Balasuriya UB. Assessment of correlation between in vitro CD3+ T cell susceptibility to EAV infection and clinical outcome following experimental infection. Vet Microbiol 157:220–225.
    doi: 10.1016/j.vetmic.2011.11.031pubmed: 22177968google scholar: lookup
  23. 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 112:207–211.
    doi: 10.1016/S0021-9975(05)80062-3pubmed: 7769149google scholar: lookup
  24. Timoney PJ, McCollum WH, Roberts AW, Murphy TW. Demonstration of the carrier state in naturally acquired equine arteritis virus infection in the stallion. Res Vet Sci 41:279–280.
    pubmed: 3022363
  25. 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 35:95–102.
    pubmed: 2824772
  26. Balasuriya UB, Hedges JF, Smalley VL, Navarrette A, McCollum WH, Timoney PJ, Snijder EJ, MacLachlan NJ. Genetic characterization of equine arteritis virus during persistent infection of stallions. J Gen Virol 85:379–390.
    doi: 10.1099/vir.0.19545-0pubmed: 14769895google scholar: lookup
  27. Balasuriya UBR, Sarkar S, Carossino M, Go YY, Chelvarajan L, Cook RF, Loynachan AT, Timoney PJ, Bailey E. Host factors that contribute to equine arteritis virus persistence in the stallion: an update. J Equine Vet Sci 43 (Suppl):S11–S17.
  28. Timoney PJ, McCollum WH. Equine viral arteritis: further characterization of the carrier state in stallions. J Reprod Fertil Suppl 56:3–11.
    pubmed: 20681110
  29. Miszczak F, Legrand L, Balasuriya UB, Ferry-Abitbol B, Zhang J, Hans A, Fortier G, Pronost S, Vabret A. Emergence of novel equine arteritis virus (EAV) variants during persistent infection in the stallion: origin of the 2007 French EAV outbreak was linked to an EAV strain present in the semen of a persistently infected carrier stallion. Virology 423:165–174.
    doi: 10.1016/j.virol.2011.11.028pubmed: 22209234google scholar: lookup
  30. Hedges JF, Balasuriya UB, Timoney PJ, McCollum WH, MacLachlan NJ. Genetic divergence with emergence of novel phenotypic variants of equine arteritis virus during persistent infection of stallions. J Virol 73:3672–3681.
    pmc: PMC104142pubmed: 10196259
  31. Zhang J, Timoney PJ, Shuck KM, Seoul G, Go YY, Lu Z, Powell DG, Meade BJ, Balasuriya UB. Molecular epidemiology and genetic characterization of equine arteritis virus isolates associated with the 2006-2007 multi-state disease occurrence in the USA. J Gen Virol 91:2286–2301.
    doi: 10.1099/vir.0.019737-0pubmed: 20444993google scholar: lookup
  32. 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 111:383–388.
    doi: 10.1016/S0021-9975(05)80096-9pubmed: 7884055google scholar: lookup
  33. Dejucq N, Jegou B. Viruses in the mammalian male genital tract and their effects on the reproductive system. Microbiol Mol Biol Rev 65:208–231.
  34. McCarthy M. Zika virus was transmitted by sexual contact in Texas, health officials report. BMJ 352:i720.
    doi: 10.1136/bmj.i720pubmed: 26848011google scholar: lookup
  35. McCarthy M. US health officials investigate sexually transmitted Zika virus infections. BMJ 352:i1180.
    doi: 10.1136/bmj.i1180pubmed: 26921165google scholar: lookup
  36. Hills SL, Russell K, Hennessey M, Williams C, Oster AM, Fischer M, Mead P. Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission—continental United States, 2016. MMWR Morb Mortal Wkly Rep 65:215–216.
    doi: 10.15585/mmwr.mm6508e2pubmed: 26937739google scholar: lookup
  37. Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis 21:359–361.
    doi: 10.3201/eid2102.141363pmc: PMC4313657pubmed: 25625872google scholar: lookup
  38. Barzon L, Pacenti M, Franchin E, Lavezzo E, Trevisan M, Sgarabotto D, Palu G. Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016. Euro Surveill 21:30316.
  39. Go YY, Bailey E, Timoney PJ, Shuck KM, Balasuriya UB. Evidence that in vitro susceptibility of CD3+ T lymphocytes to equine arteritis virus infection reflects genetic predisposition of naturally infected stallions to become carriers of the virus. J Virol 86:12407–12410.
    doi: 10.1128/JVI.01698-12pmc: PMC3486460pubmed: 22933293google scholar: lookup
  40. Go YY, Zhang J, Timoney PJ, Cook RF, Horohov DW, Balasuriya UB. 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 84:4898–4911.
    doi: 10.1128/JVI.02743-09pmc: PMC2863813pubmed: 20219931google scholar: lookup
  41. Go YY, Bailey E, Cook DG, Coleman SJ, Macleod JN, Chen KC, Timoney PJ, Balasuriya UB. 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 85:13174–13184.
    doi: 10.1128/JVI.06068-11pmc: PMC3233183pubmed: 21994447google scholar: lookup
  42. Sarkar S, Bailey E, Go YY, Cook RF, Kalbfleisch T, Eberth J, Chelvarajan RL, Shuck KM, Artiushin S, Timoney PJ, Balasuriya UB. 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 12:e1006467.
  43. 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 109:29–46.
  44. Danilenko DM, Rossitto PV, Van der Vieren M, Le Trong H, McDonough SP, Affolter VK, Moore PF. A novel canine leukointegrin, alpha d beta 2, is expressed by specific macrophage subpopulations in tissue and a minor CD8+ lymphocyte subpopulation in peripheral blood. J Immunol 155:35–44.
    pubmed: 7541420
  45. Moore PF, Rossitto PV, Danilenko DM. Canine leukocyte integrins: characterization of a CD18 homologue. Tissue Antigens 36:211–220.
  46. Danilenko DM, Moore PF, Rossitto PV. Canine leukocyte cell adhesion molecules (LeuCAMs): characterization of the CD11/CD18 family. Tissue Antigens 40:13–21.
  47. Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 57:1–9.
    doi: 10.1016/S0169-328X(98)00040-0pubmed: 9630473google scholar: lookup
  48. Ahmed Z, Shaw G, Sharma VP, Yang C, McGowan E, Dickson DW. Actin-binding proteins coronin-1a and IBA-1 are effective microglial markers for immunohistochemistry. J Histochem Cytochem 55:687–700.
    doi: 10.1369/jhc.6A7156.2007pubmed: 17341475google scholar: lookup
  49. Deininger MH, Meyermann R, Schluesener HJ. The allograft inflammatory factor-1 family of proteins. FEBS Lett 514:115–121.
    doi: 10.1016/S0014-5793(02)02430-4pubmed: 11943136google scholar: lookup
  50. Nakayama M. Antigen presentation by MHC-dressed cells. Front Immunol 5:672.
    doi: 10.3389/fimmu.2014.00672pmc: PMC4283639pubmed: 25601867google scholar: lookup
  51. Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology 210:153–160.
    doi: 10.1016/j.imbio.2005.05.010pubmed: 16164022google scholar: lookup
  52. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737.
    doi: 10.1038/nri3073pmc: PMC3422549pubmed: 21997792google scholar: lookup
  53. Chavez-Galan L, Olleros ML, Vesin D, Garcia I. Much more than M1 and M2 macrophages, there are also CD169+ and TCR+ macrophages. Front Immunol 6:263.
    doi: 10.3389/fimmu.2015.00263pmc: PMC4443739pubmed: 26074923google scholar: lookup
  54. Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, Miyashita T, Tajima H, Ninomiya I, Munesue S, Harashima A, Harada S, Yamamoto H, Ohta T. Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination. Gastric Cancer 19:1052–1065.
    doi: 10.1007/s10120-015-0579-8pmc: PMC5034006pubmed: 26621525google scholar: lookup
  55. Rugtveit J, Scott H, Halstensen TS, Norstein J, Brandtzaeg P. Expression of the L1 antigen (calprotectin) by tissue macrophages reflects recent recruitment from peripheral blood rather than upregulation of local synthesis: implications for rejection diagnosis in formalin-fixed kidney specimens. J Pathol 180:194–199.
  56. Grosche A, Morton AJ, Polyak MM, Matyjaszek S, Freeman DE. Detection of calprotectin and its correlation to the accumulation of neutrophils within equine large colon during ischaemia and reperfusion. Equine Vet J 40:393–399.
    doi: 10.2746/042516408X302500pubmed: 18487110google scholar: lookup
  57. Alvarez B, Sanchez C, Bullido R, Marina A, Lunney J, Alonso F, Ezquerra A, Dominguez J. A porcine cell surface receptor identified by monoclonal antibodies to SWC3 is a member of the signal regulatory protein family and associates with protein-tyrosine phosphatase SHP-1. Tissue Antigens 55:342–351.
  58. Herrmann-Hoesing LM, Noh SM, Snekvik KR, White SN, Schneider DA, Truscott T, Knowles DP. Ovine progressive pneumonia virus capsid antigen as found in CD163- and CD172a-positive alveolar macrophages of persistently infected sheep. Vet Pathol 47:518–528.
    doi: 10.1177/0300985809359605pubmed: 20382821google scholar: lookup
  59. Gulbahar MY, Davis WC, Yuksel H, Cabalar M. Immunohistochemical evaluation of inflammatory infiltrate in the skin and lung of lambs naturally infected with sheeppox virus. Vet Pathol 43:67–75.
    doi: 10.1354/vp.43-1-67pubmed: 16407491google scholar: lookup
  60. Nalubamba KS, Gossner AG, Dalziel RG, Hopkins J. Differential expression of pattern recognition receptors in sheep tissues and leukocyte subsets. Vet Immunol Immunopathol 118:252–262.
    doi: 10.1016/j.vetimm.2007.05.018pubmed: 17604125google scholar: lookup
  61. van Beek EM, Cochrane F, Barclay AN, van den Berg TK. Signal regulatory proteins in the immune system. J Immunol 175:7781–7787.
    doi: 10.4049/jimmunol.175.12.7781pubmed: 16339510google scholar: lookup
  62. McNeilly TN, Brown JK, Harkiss G. Differential expression of cell surface markers by ovine respiratory tract dendritic cells. J Histochem Cytochem 54:1021–1030.
    doi: 10.1369/jhc.6A6940.2006pubmed: 16651390google scholar: lookup
  63. Aerts-Toegaert C, Heirman C, Tuyaerts S, Corthals J, Aerts JL, Bonehill A, Thielemans K, Breckpot K. CD83 expression on dendritic cells and T cells: correlation with effective immune responses. Eur J Immunol 37:686–695.
    doi: 10.1002/eji.200636535pubmed: 17301951google scholar: lookup
  64. Ni K, O'Neill HC. The role of dendritic cells in T cell activation. Immunol Cell Biol 75:223–230.
    doi: 10.1038/icb.1997.35pubmed: 9243286google scholar: lookup
  65. Bimczok D, Rothkotter HJ. Lymphocyte migration studies. Vet Res 37:325–338.
    doi: 10.1051/vetres:2006004pubmed: 16611551google scholar: lookup
  66. Di Carlo E, Magnasco S, D'Antuono T, Tenaglia R, Sorrentino C. The prostate-associated lymphoid tissue (PALT) is linked to the expression of homing chemokines CXCL13 and CCL21. Prostate 67:1070–1080.
    doi: 10.1002/pros.20604pubmed: 17474076google scholar: lookup
  67. Fritz FJ, Westermann J, Pabst R. The mucosa of the male genital tract; part of the common mucosal secretory immune system?. Eur J Immunol 19:475–479.
    doi: 10.1002/eji.1830190310pubmed: 2785042google scholar: lookup
  68. Fu H, Ward EJ, Marelli-Berg FM. Mechanisms of T cell organotropism. Cell Mol Life Sci 73:3009–3033.
    doi: 10.1007/s00018-016-2211-4pmc: PMC4951510pubmed: 27038487google scholar: lookup
  69. Nguyen PV, Kafka JK, Ferreira VH, Roth K, Kaushic C. Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection. Cell Mol Immunol 11:410–427.
    doi: 10.1038/cmi.2014.41pmc: PMC4197208pubmed: 24976268google scholar: lookup
  70. Zaneveld LJD, Anderson DJ, Whaley KJ, Quayle AJ. 1996. Appendix D, barrier methods and mucosal immunologic approaches, p 430–473. In Harrison PF, Rosenfield A (ed), Contraceptive research and development: looking to the future. National Academies Press, Washington, DC.
    pubmed: 25121263
  71. Vairo S, Van den Broeck W, Favoreel H, Scagliarini A, Nauwynck H. Development and use of a polarized equine upper respiratory tract mucosal explant system to study the early phase of pathogenesis of a European strain of equine arteritis virus. Vet Res 44:22.
    doi: 10.1186/1297-9716-44-22pmc: PMC3668984pubmed: 23537375google scholar: lookup
  72. Carossino M, Loynachan AT, James MacLachlan N, Drew C, Shuck KM, Timoney PJ, Del Piero F, Balasuriya UB. Detection of equine arteritis virus by two chromogenic RNA in situ hybridization assays (conventional and RNAscope (®) and assessment of their performance in tissues from aborted equine fetuses. Arch Virol 161:3125–3136.
    doi: 10.1007/s00705-016-3014-5pubmed: 27541817google scholar: lookup
  73. Del Piero F, Wilkins PA, Lopez JW, Glaser AL, Dubovi EJ, Schlafer DH, Lein DH. Equine viral arteritis in newborn foals: clinical, pathological, serological, microbiological and immunohistochemical observations. Equine Vet J 29:178–185.
  74. Cecere TE, Todd SM, Leroith T. Regulatory T cells in arterivirus and coronavirus infections: do they protect against disease or enhance it?. Viruses 4:833–846.
    doi: 10.3390/v4050833pmc: PMC3386620pubmed: 22754651google scholar: lookup
  75. Veiga-Parga T, Sehrawat S, Rouse BT. Role of regulatory T cells during virus infection. Immunol Rev 255:182–196.
    doi: 10.1111/imr.12085pmc: PMC3748387pubmed: 23947355google scholar: lookup
  76. Wongyanin P, Buranapraditkul S, Yoo D, Thanawongnuwech R, Roth JA, Suradhat S. Role of porcine reproductive and respiratory syndrome virus nucleocapsid protein in induction of interleukin-10 and regulatory T-lymphocytes (Treg). J Gen Virol 93:1236–1246.
    doi: 10.1099/vir.0.040287-0pubmed: 22422061google scholar: lookup
  77. Silva-Campa E, Mata-Haro V, Mateu E, Hernandez J. Porcine reproductive and respiratory syndrome virus induces CD4+ CD8+ CD25+ Foxp3+ regulatory T cells (Tregs). Virology 430:73–80.
    doi: 10.1016/j.virol.2012.04.009pubmed: 22609353google scholar: lookup
  78. Cecere TE, Meng XJ, Pelzer K, Todd SM, Beach NM, Ni YY, Leroith T. Co-infection of porcine dendritic cells with porcine circovirus type 2a (PCV2a) and genotype II porcine reproductive and respiratory syndrome virus (PRRSV) induces CD4+ CD25+ FoxP3+ T cells in vitro. Vet Microbiol 160:233–239.
  79. Gomez-Laguna J, Rodriguez-Gomez IM, Barranco I, Pallares FJ, Salguero FJ, Carrasco L. Enhanced expression of TGFβ protein in lymphoid organs and lung, but not in serum, of pigs infected with a European field isolate of porcine reproductive and respiratory syndrome virus. Vet Microbiol 158:187–193.
  80. Kahan SM, Wherry EJ, Zajac AJ. T cell exhaustion during persistent viral infections. Virology 479–480:180–193.
    doi: 10.1016/j.virol.2014.12.033pmc: PMC4424083pubmed: 25620767google scholar: lookup
  81. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 15:486–499.
    doi: 10.1038/nri3862pmc: PMC4889009pubmed: 26205583google scholar: lookup
  82. Zuniga EI, Macal M, Lewis GM, Harker JA. Innate and adaptive immune regulation during chronic viral infections. Annu Rev Virol 2:573–597.
  83. Wherry EJ. T cell exhaustion. Nat Immunol 12:492–499.
    pubmed: 21739672
  84. Klenerman P, Hill A. T cells and viral persistence: lessons from diverse infections. Nat Immunol 6:873–879.
    doi: 10.1038/ni1241pubmed: 16116467google scholar: lookup
  85. Roved J, Westerdahl H, Hasselquist D. Sex differences in immune responses: hormonal effects, antagonistic selection, and evolutionary consequences. Horm Behav 88:95–105.
    doi: 10.1016/j.yhbeh.2016.11.017pubmed: 27956226google scholar: lookup
  86. Miszczak F, Shuck KM, Lu Z, Go YY, Zhang J, Sells S, Vabret A, Pronost S, Fortier G, Timoney PJ, Balasuriya UB. Evaluation of two magnetic-bead-based viral nucleic acid purification kits and three real-time reverse transcription-PCR reagent systems in two TaqMan assays for equine arteritis virus detection in semen. J Clin Microbiol 49:3694–3696.
    doi: 10.1128/JCM.01187-11pmc: PMC3187312pubmed: 21832018google scholar: lookup
  87. Carossino M, Lee PA, Nam B, Skillman A, Shuck KM, Timoney PJ, Tsai Y, Ma L, Chang HG, Wang HT, Balasuriya UBR. Development and evaluation of a reverse transcription-insulated isothermal polymerase chain reaction (RT-iiPCR) assay for detection of equine arteritis virus in equine semen and tissue samples using the POCKIT system. J Virol Methods 234:7–15.
  88. Pacheco JM, Smoliga GR, O'Donnell V, Brito BP, Stenfeldt C, Rodriguez LL, Arzt J. Persistent foot-and-mouth disease virus infection in the nasopharynx of cattle; tissue-specific distribution and local cytokine expression. PLoS One 10:e0125698.
  89. Stenfeldt C, Eschbaumer M, Rekant SI, Pacheco JM, Smoliga GR, Hartwig EJ, Rodriguez LL, Arzt J. The foot-and-mouth disease carrier state divergence in cattle. J Virol 90:6344–6364.
    doi: 10.1128/JVI.00388-16pmc: PMC4936139pubmed: 27147736google scholar: lookup
  90. Stenfeldt C, Pacheco JM, Smoliga GR, Bishop E, Pauszek SJ, Hartwig EJ, Rodriguez LL, Arzt J. Detection of foot-and-mouth disease virus RNA and capsid protein in lymphoid tissues of convalescent pigs does not indicate existence of a carrier state. Transbound Emerg Dis 63:152–164.
    doi: 10.1111/tbed.12235pubmed: 24943477google scholar: lookup
  91. Prabhudas M, Bowdish D, Drickamer K, Febbraio M, Herz J, Kobzik L, Krieger M, Loike J, Means TK, Moestrup SK, Post S, Sawamura T, Silverstein S, Wang XY, El Khoury J. Standardizing scavenger receptor nomenclature. J Immunol 192:1997–2006.
    doi: 10.4049/jimmunol.1490003pmc: PMC4238968pubmed: 24563502google scholar: lookup
  92. Sarkar S, Chelvarajan L, Go YY, Cook F, Artiushin S, Mondal S, Anderson K, Eberth J, Timoney PJ, Kalbfleisch TS, Bailey E, Balasuriya UB. Equine arteritis virus uses equine CXCL16 as an entry receptor. J Virol 90:3366–3384.
    doi: 10.1128/JVI.02455-15pmc: PMC4794689pubmed: 26764004google scholar: lookup
  93. Izquierdo MC, Martin-Cleary C, Fernandez-Fernandez B, Elewa U, Sanchez-Nino MD, Carrero JJ, Ortiz A. CXCL16 in kidney and cardiovascular injury. Cytokine Growth Factor Rev 25:317–325.
    doi: 10.1016/j.cytogfr.2014.04.002pubmed: 24861945google scholar: lookup
  94. Morgan AJ, Guillen C, Symon FA, Huynh TT, Berry MA, Entwisle JJ, Briskin M, Pavord ID, Wardlaw AJ. Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease. Clin Exp Allergy 35:1572–1580.
  95. Richardsen E, Ness N, Melbo-Jorgensen C, Johannesen C, Grindstad T, Nordbakken C, Al-Saad S, Andersen S, Donnem T, Nordby Y, Bremnes RM, Busund LT. The prognostic significance of CXCL16 and its receptor C-X-C chemokine receptor 6 in prostate cancer. Am J Pathol 185:2722–2730.
    doi: 10.1016/j.ajpath.2015.06.013pubmed: 26272362google scholar: lookup
  96. Shashkin P, Simpson D, Mishin V, Chesnutt B, Ley K. Expression of CXCL16 in human T cells. Arterioscler Thromb Vasc Biol 23:148–149.
  97. Nakayama T, Hieshima K, Izawa D, Tatsumi Y, Kanamaru A, Yoshie O. Cutting edge: profile of chemokine receptor expression on human plasma cells accounts for their efficient recruitment to target tissues. J Immunol 170:1136–1140.
    doi: 10.4049/jimmunol.170.3.1136pubmed: 12538668google scholar: lookup
  98. Gunther C, Carballido-Perrig N, Kaesler S, Carballido JM, Biedermann T. CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells. J Investig Dermatol 132:626–634.
    doi: 10.1038/jid.2011.371pubmed: 22113484google scholar: lookup
  99. van der Voort R, van Lieshout AW, Toonen LW, Sloetjes AW, van den Berg WB, Figdor CG, Radstake TR, Adema GJ. Elevated CXCL16 expression by synovial macrophages recruits memory T cells into rheumatoid joints. Arthritis Rheum 52:1381–1391.
    doi: 10.1002/art.21004pubmed: 15880344google scholar: lookup
  100. Hedges JF, Demaula CD, Moore BD, McLaughlin BE, Simon SI, MacLachlan NJ. Characterization of equine E-selectin. Immunology 103:498–504.
  101. Timoney PJ, McCollum WH, Roberts AW, McDonald MJ. Status of equine viral arteritis in Kentucky, 1985. J Am Vet Med Assoc 191:36–39.
    pubmed: 3038806
  102. World Organisation for Animal Health (OIE). Equine viral arteritis, chapter 2.5.10. Manual of diagnostic tests and vaccines for terrestrial animals 7th ed, vol 2.
  103. Campos JR, Breheny P, Araujo RR, Troedsson MH, Squires EL, Timoney PJ, Balasuriya UB. Semen quality of stallions challenged with the Kentucky 84 strain of equine arteritis virus. Theriogenology 82:1068–1079.
  104. Balasuriya UB, Leutenegger CM, Topol JB, McCollum WH, Timoney PJ, MacLachlan NJ. Detection of equine arteritis virus by real-time TaqMan reverse transcription-PCR assay. J Virol Methods 101:21–28.
    doi: 10.1016/S0166-0934(01)00416-5pubmed: 11849680google scholar: lookup
  105. Heidner HW, Rossitto PV, MacLachlan NJ. Identification of four distinct neutralizing epitopes on bluetongue virus serotype 10 using neutralizing monoclonal antibodies and neutralization-escape variants. Virology 176:658–661.
    doi: 10.1016/0042-6822(90)90041-Opubmed: 1693250google scholar: lookup
  106. Jensen EC. Quantitative analysis of histological staining and fluorescence using ImageJ. Anat Rec (Hoboken) 296:378–381.
    doi: 10.1002/ar.22641pubmed: 23382140google scholar: lookup
  107. Landini G. Colour deconvolution. .
  108. Gown AM, Goldstein LC, Barry TS, Kussick SJ, Kandalaft PL, Kim PM, Tse CC. High concordance between immunohistochemistry and fluorescence in situ hybridization testing for HER2 status in breast cancer requires a normalized IHC scoring system. Mod Pathol 21:1271–1277.
    doi: 10.1038/modpathol.2008.83pubmed: 18487992google scholar: lookup
  109. Tumas DB, Brassfield AL, Travenor AS, Hines MT, Davis WC, McGuire TC. Monoclonal antibodies to the equine CD2 T lymphocyte marker, to a pan-granulocyte/monocyte marker and to a unique pan-B lymphocyte marker. Immunobiology 192:48–64.
    doi: 10.1016/S0171-2985(11)80407-9pubmed: 7750989google scholar: lookup
  110. Liu C, Cook FR, Cook SJ, Craigo JK, Even DL, Issel CJ, Montelaro RC, Horohov DW. The determination of in vivo envelope-specific cell-mediated immune responses in equine infectious anemia virus-infected ponies. Vet Immunol Immunopathol 148:302–310.
  111. Blanchard-Channell M, Moore PF, Stott JL. Characterization of monoclonal antibodies specific for equine homologues of CD3 and CD5. Immunology 82:548–554.
    pmc: PMC1414917pubmed: 7530685
  112. Lunn DP, Holmes MA, Duffus WP. Three monoclonal antibodies identifying antigens on all equine T lymphocytes, and two mutually exclusive T-lymphocyte subsets. Immunology 74:251–257.
    pmc: PMC1384601pubmed: 1748472
  113. Crump AL, Davis W, Antczak DF. A monoclonal antibody identifying a T-cell marker in the horse. Anim Genet 19:349–357.
    pubmed: 3069011
  114. Boliar S, Chambers TM. A new strategy of immune evasion by influenza A virus: inhibition of monocyte differentiation into dendritic cells. Vet Immunol Immunopathol 136:201–210.
    doi: 10.1016/j.vetimm.2010.03.004pubmed: 20356633google scholar: lookup
  115. Yamate J, Yoshida H, Tsukamoto Y, Ide M, Kuwamura M, Ohashi F, Miyamoto T, Kotani T, Sakuma S, Takeya M. Distribution of cells immunopositive for AM-3K, a novel monoclonal antibody recognizing human macrophages, in normal and diseased tissues of dogs, cats, horses, cattle, pigs, and rabbits. Vet Pathol 37:168–176.
    doi: 10.1354/vp.37-2-168pubmed: 10714646google scholar: lookup
  116. Tomokiyo R, Jinnouchi K, Honda M, Wada Y, Hanada N, Hiraoka T, Suzuki H, Kodama T, Takahashi K, Takeya M. Production, characterization, and interspecies reactivities of monoclonal antibodies against human class A macrophage scavenger receptors. Atherosclerosis 161:123–132.
    doi: 10.1016/S0021-9150(01)00624-4pubmed: 11882324google scholar: lookup
  117. Merant C, Bonnefont C, Desbos A, Greenland T, Cadore JL, Monier JC. Cross-species reactivity of seven monoclonal antibodies with equine lymphocytes by flow cytometry. Vet Res 34:791–801.
    doi: 10.1051/vetres:2003033pubmed: 14746773google scholar: lookup
  118. Hirayama K, Honda Y, Sako T, Okamoto M, Tsunoda N, Tagami M, Taniyama H. Invasive ductal carcinoma of the mammary gland in a mare. Vet Pathol 40:86–91.
    doi: 10.1354/vp.40-1-86pubmed: 12627717google scholar: lookup
  119. Bohn W, Wiegers W, Beuttenmuller M, Traub P. Species-specific recognition patterns of monoclonal antibodies directed against vimentin. Exp Cell Res 201:1–7.
    doi: 10.1016/0014-4827(92)90341-5pubmed: 1612114google scholar: lookup

Citations

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  1. Thieulent CJ, Sarkar S, Carossino M, Bhowmik M, Zhu H, Balasuriya UBR. Cell Surface Vimentin Is an Attachment Factor That Facilitates Equine Arteritis Virus Infection In Vitro. Viruses 2026 Jan 15;18(1).
    doi: 10.3390/v18010113pubmed: 41600875google scholar: lookup
  2. Yan B, Guo J, Lai W, Chen Y, Wang Z, Peng Y, Chang S. The multifaceted roles of ribosomal P complex in cancer. World J Surg Oncol 2025 Oct 21;23(1):388.
    doi: 10.1186/s12957-025-04014-7pubmed: 41121305google scholar: lookup
  3. Maloney SM, Shaw TM, Nennig KM, Larsen MS, Shah A, Kumar A, Marcotrigiano J, Grove J, Snijder EJ, Kirchdoerfer RN, Bailey AL. CD81 is a receptor for equine arteritis virus (family: Arteriviridae). mBio 2025 Jul 9;16(7):e0062325.
    doi: 10.1128/mbio.00623-25pubmed: 40422661google scholar: lookup
  4. Durazo-Martínez K, Osorio FA, Delhon G, Hernández J, Vu HLX. New insights into the testicular tropism of porcine reproductive and respiratory syndrome virus. Microbiol Spectr 2025 Apr;13(4):e0296424.
    doi: 10.1128/spectrum.02964-24pubmed: 39969185google scholar: lookup
  5. Lee J, Mordoh S, Mirza M, Carossino M, Del Piero F. Acute myeloid leukemia-M1 in a horse with neurologic signs and necrotizing enterocolitis. J Vet Diagn Invest 2024 Nov;36(6):836-841.
    doi: 10.1177/10406387241268322pubmed: 39233385google scholar: lookup
  6. Thieulent CJ, Carossino M, Balasuriya UBR, Graves K, Bailey E, Eberth J, Canisso IF, Andrews FM, Keowen ML, Go YY. 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.2022.871875pubmed: 35495124google scholar: lookup
  7. Uche IK, Fowlkes N, Vu L, Watanabe T, Carossino M, Nabi R, Del Piero F, Rudd JS, Kousoulas KG, Rider PJF. Novel Oncolytic Herpes Simplex Virus 1 VC2 Promotes Long-Lasting, Systemic Anti-melanoma Tumor Immune Responses and Increased Survival in an Immunocompetent B16F10-Derived Mouse Melanoma Model. J Virol 2021 Jan 13;95(3).
    doi: 10.1128/JVI.01359-20pubmed: 33177208google scholar: lookup
  8. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Cook RF, Timoney PJ, Balasuriya UBR. Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis. PLoS Pathog 2019 Jul;15(7):e1007950.
    doi: 10.1371/journal.ppat.1007950pubmed: 31356622google scholar: lookup
  9. Butler JE, Sinkora M, Wang G, Stepanova K, Li Y, Cai X. Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis. Front Immunol 2019;10:1077.
    doi: 10.3389/fimmu.2019.01077pubmed: 31156633google scholar: lookup
  10. Nam B, Mekuria Z, Carossino M, Li G, Zheng Y, Zhang J, Cook RF, Shuck KM, Campos JR, Squires EL, Troedsson MHT, Timoney PJ, Balasuriya UBR. Intrahost Selection Pressure Drives Equine Arteritis Virus Evolution during Persistent Infection in the Stallion Reproductive Tract. J Virol 2019 Jun 15;93(12).
    doi: 10.1128/JVI.00045-19pubmed: 30918077google scholar: lookup
  11. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Shuck KM, Timoney PJ, Cook RF, Balasuriya UBR. 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 May 1;92(9).
    doi: 10.1128/JVI.00015-18pubmed: 29444949google scholar: lookup
  12. Perry DL, Huzella LM, Bernbaum JG, Holbrook MR, Jahrling PB, Hagen KR, Schnell MJ, Johnson RF. Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease. Am J Pathol 2018 Mar;188(3):550-558.
    doi: 10.1016/j.ajpath.2017.11.004pubmed: 29429544google scholar: lookup
  13. Carossino M, Wagner B, Loynachan AT, Cook RF, Canisso IF, Chelvarajan L, Edwards CL, Nam B, Timoney JF, Timoney PJ, Balasuriya UBR. Equine Arteritis Virus Elicits a Mucosal Antibody Response in the Reproductive Tract of Persistently Infected Stallions. Clin Vaccine Immunol 2017 Oct;24(10).
    doi: 10.1128/CVI.00215-17pubmed: 28814389google scholar: lookup