1887

Abstract

The ancestral equine herpesvirus 1 (EHV1), closely related to human herpes viruses, exploits leukocytes to reach its target organs, accordingly evading the immune surveillance system. Circulating EHV1 strains can be divided into abortigenic/neurovirulent, causing reproductive/neurological disorders. Neurovirulent EHV1 more efficiently recruits monocytic CD172a cells to the upper respiratory tract (URT), while abortigenic EHV1 tempers monocyte migration. Whether similar results could be expected for T lymphocytes is not known. Therefore, we questioned whether differences in T cell recruitment could be associated with variations in cell tropism between both EHV1 phenotypes, and which viral proteins might be involved. The expression of CXCL9 and CXCL10 was evaluated in abortigenic/neurovirulent EHV1-inoculated primary respiratory epithelial cells (ERECs). The bioactivity of chemokines was tested with a functional migration assay. Replication of neurovirulent EHV1 in the URT resulted in an enhanced expression/bioactivity of CXCL9 and CXCL10, compared to abortigenic EHV1. Interestingly, deletion of glycoprotein 2 resulted in an increased recruitment of both monocytic CD172a cells and T lymphocytes to the corresponding EREC supernatants. Our data reveal a novel function of EHV1-gp2, tempering leukocyte migration to the URT, further indicating a sophisticated virus-mediated orchestration of leukocyte recruitment to the URT.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001317
2019-11-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/100/11/1567.html?itemId=/content/journal/jgv/10.1099/jgv.0.001317&mimeType=html&fmt=ahah

References

  1. Griffith JW, Sokol CL, Luster AD. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol 2014; 32:659–702 [View Article]
    [Google Scholar]
  2. Stone M, Hayward J, Huang C, E. Huma Z, Sanchez J. Mechanisms of regulation of the chemokine-receptor network. Int J Mol Sci 2017; 18:342 [View Article]
    [Google Scholar]
  3. Reinhart TA, Qin S, Sui Y. Multiple roles for chemokines in the pathogenesis of SIV infection. Curr HIV Res 2009; 7:73–82 [View Article]
    [Google Scholar]
  4. Nibbs RJB, Graham GJ. Immune regulation by atypical chemokine receptors. Nat Rev Immunol 2013; 13:815–829 [View Article]
    [Google Scholar]
  5. Abendroth A, Morrow G, Cunningham AL, Slobedman B. Varicella-Zoster virus infection of human dendritic cells and transmission to T cells: implications for virus dissemination in the host. J Virol 2001; 75:6183–6192 [View Article]
    [Google Scholar]
  6. Suresh P, Wanchu A. Chemokines and chemokine receptors in HIV infection: role in pathogenesis and therapeutics. J Postgrad Med 2006; 52:210–217
    [Google Scholar]
  7. Schaller M, Hogaboam CM, Lukacs N, Kunkel SL. Respiratory viral infections drive chemokine expression and exacerbate the asthmatic response. J Allergy Clin Immunol 2006; 118:295–302 [View Article]
    [Google Scholar]
  8. Leoni V, Gianni T, Salvioli S, Campadelli-Fiume G. Herpes simplex virus glycoproteins gH/gL and gB bind Toll-like receptor 2, and soluble gH/gL is sufficient to activate NF-κB. J Virol 2012; 86:6555–6562 [View Article]
    [Google Scholar]
  9. Paludan SR, Bowie AG, Horan KA, Fitzgerald KA. Recognition of herpesviruses by the innate immune system. Nat Rev Immunol 2011; 11:143–154 [View Article]
    [Google Scholar]
  10. Bonnet MC, Weil R, Dam E, Hovanessian AG, Meurs EF. Pkr stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex. Mol Cell Biol 2000; 20:4532–4542 [View Article]
    [Google Scholar]
  11. Zamanian-Daryoush M, Mogensen TH, DiDonato JA, Williams BR. Nf-Kappab activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase. Mol Cell Biol 2000; 20:1278–1290 [View Article]
    [Google Scholar]
  12. Gil J, García MA, Gomez-Puertas P, Guerra S, Rullas J et al. Traf family proteins link PKR with NF-kappa B activation. Mol Cell Biol 2004; 24:4502–4512 [View Article]
    [Google Scholar]
  13. Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol 2006; 7:131–137 [View Article]
    [Google Scholar]
  14. Huse M, Lillemeier BF, Kuhns MS, Chen DS, Davis MM. T cells use two directionally distinct pathways for cytokine secretion. Nat Immunol 2006; 7:247–255 [View Article]
    [Google Scholar]
  15. Olson TS, Ley K. Chemokines and chemokine receptors in leukocyte trafficking. Am J Physiol Regul Integr Comp Physiol 2002; 283:R7–R28 [View Article]
    [Google Scholar]
  16. Bukowski JF, Welsh RM. The role of natural killer cells and interferon in resistance to acute infection of mice with herpes simplex virus type 1. Journal of immunology 1986; 136:3481–3485
    [Google Scholar]
  17. Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA. Pattern recognition receptors and the innate immune response to viral infection. Viruses 2011; 3:920–940 [View Article]
    [Google Scholar]
  18. Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 2015; 7:a016303 [View Article]
    [Google Scholar]
  19. Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 1999; 17:189–220 [View Article]
    [Google Scholar]
  20. Trinchieri G. Biology of natural killer cells. Adv Immunol 1989; 47:187–376
    [Google Scholar]
  21. Mackay CR. Chemokines: immunology's high impact factors. Nat Immunol 2001; 2:95–101 [View Article]
    [Google Scholar]
  22. Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke. Arch Virol 1986; 90:111–124 [View Article]
    [Google Scholar]
  23. Crabb BS, Studdert MJ. Equine herpesviruses 4 (equine rhinopneumonitis virus) and 1 (equine abortion virus). Adv Virus Res 1995; 45:153–190
    [Google Scholar]
  24. Gryspeerdt AC, Vandekerckhove AP, Garré B, Barbé F, Van de Walle GR et al. Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses. Vet Microbiol 2010; 142:242–253 [View Article]
    [Google Scholar]
  25. Vandekerckhove AP, Glorieux S, Gryspeerdt AC, Steukers L, Duchateau L et al. Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants. J Gen Virol 2010; 91:2019–2028 [View Article]
    [Google Scholar]
  26. Bryans JT, Allen GP. Herpesviral Diseases of the Horse. In Wittmann G. (editors) Herpesvirus Diseases of Cattle, Horses, and Pigs Boston, MA: Springer US; 1989 pp 176–229
    [Google Scholar]
  27. Goehring LS, van Winden SC, van Maanen C, Sloet van Oldruitenborgh-Oosterbaan MM. Equine herpesvirus type 1-associated myeloencephalopathy in the Netherlands: a four-year retrospective study (1999-2003). J Vet Intern Med 2006; 20:601–607 [View Article]
    [Google Scholar]
  28. Goehring LS, Hussey GS, Ashton LV, Schenkel AR, Lunn DP. Infection of central nervous system endothelial cells by cell-associated EHV-1. Vet Microbiol 2011; 148:389–395 [View Article]
    [Google Scholar]
  29. Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z et al. Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks. J Virol 2006; 80:4047–4060 [View Article]
    [Google Scholar]
  30. Laval K, Favoreel HW, Nauwynck HJ. Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases. J Gen Virol 2015; 96:118–130 [View Article]
    [Google Scholar]
  31. Laval K, Van Cleemput J, Poelaert KC, Brown IK, Nauwynck HJ. Replication of neurovirulent equine herpesvirus type 1 (EHV-1) in CD172a+ monocytic cells. Comp Immunol Microbiol Infect Dis 2017; 50:58–62 [View Article]
    [Google Scholar]
  32. Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Soboll Hussey G et al. Abortigenic but not neurotropic equine herpes virus 1 modulates the interferon antiviral defense. Front Cell Infect Microbiol 2018; 8:312 [View Article]
    [Google Scholar]
  33. Zhao J, Poelaert KCK, Van Cleemput J, Nauwynck HJ. Ccl2 and CCL5 driven attraction of CD172a+ monocytic cells during an equine herpesvirus type 1 (EHV-1) infection in equine nasal mucosa and the impact of two migration inhibitors, rosiglitazone (RSG) and quinacrine (Qc). Vet Res 2017; 48: [View Article]
    [Google Scholar]
  34. Holz CL, Nelli RK, Wilson ME, Zarski LM, Azab W et al. Viral genes and cellular markers associated with neurological complications during herpesvirus infections. J Gen Virol 2017; 98:1439–1454 [View Article]
    [Google Scholar]
  35. Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L et al. Equine herpesvirus 1 Bridles T lymphocytes to reach its target organs. J Virol 2019; 93:JVI.02098–18 [View Article]
    [Google Scholar]
  36. Drummer HE, Studdert MJ, Crabb BS. Equine herpesvirus-4 glycoprotein G is secreted as a disulphide-linked homodimer and is present as two homodimeric species in the virion. J Gen Virol 1998; 79:1205–1213 [View Article]
    [Google Scholar]
  37. von Einem J, Smith PM, Van de Walle GR, O'Callaghan DJ, Osterrieder N. In vitro and in vivo characterization of equine herpesvirus type 1 (EHV-1) mutants devoid of the viral chemokine-binding glycoprotein G (gG). Virology 2007; 362:151–162 [View Article]
    [Google Scholar]
  38. Bannert N, Craig S, Farzan M, Sogah D, Santo NV et al. Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of CC chemokine receptor 5 contribute to high affinity binding of chemokines. J Exp Med 2001; 194:1661–1674 [View Article]
    [Google Scholar]
  39. Biacchesi S, Skiadopoulos MH, Yang L, Lamirande EW, Tran KC et al. Recombinant human metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate. J Virol 2004; 78:12877–12887 [View Article]
    [Google Scholar]
  40. Biacchesi S, Pham QN, Skiadopoulos MH, Murphy BR, Collins PL et al. Infection of nonhuman primates with recombinant human metapneumovirus lacking the SH, G, or M2-2 protein categorizes each as a nonessential accessory protein and identifies vaccine candidates. J Virol 2005; 79:12608–12613 [View Article]
    [Google Scholar]
  41. Bao X, Liu T, Shan Y, Li K, Garofalo RP et al. Human metapneumovirus glycoprotein G inhibits innate immune responses. PLoS Pathog 2008; 4:e1000077 [View Article]
    [Google Scholar]
  42. Whittaker GR, Wheldon LA, Giles LE, Stocks JM, Halliburton IW et al. Characterization of the high Mr glycoprotein (gP300) of equine herpesvirus type 1 as a novel glycoprotein with extensive O-linked carbohydrate. J Gen Virol 1990; 71:2407–2416 [View Article]
    [Google Scholar]
  43. van Der Meulen KM, Nauwynck HJ, Buddaert W, Pensaert MB. Replication of equine herpesvirus type 1 in freshly isolated equine peripheral blood mononuclear cells and changes in susceptibility following mitogen stimulation. J Gen Virol 2000; 81:21–25 [View Article]
    [Google Scholar]
  44. Studdert MJ, Simpson T, Roizman B. Differentiation of respiratory and abortigenic isolates of equine herpesvirus 1 by restriction endonucleases. Science 1981; 214:562–564 [View Article]
    [Google Scholar]
  45. Mayr A, Pette J, Petzoldt K, Wagener K. Untersuchungen Zur Entwicklung eines Lebendimpfstoffes gegen die rhinopneumonitis (Stutenabort) Der Pferde1). Zentralblatt für Veterinärmedizin Reihe B 1968; 15:406–418
    [Google Scholar]
  46. Huang J, Hartley CA, Ficorilli NP, Crabb BS, Studdert MJ. Glycoprotein G deletion mutants of equine herpesvirus 1 (EHV1; equine abortion virus) and EHV4 (equine rhinopneumonitis virus). Arch Virol 2005; 150:2583–2592 [View Article]
    [Google Scholar]
  47. Rudolph J, Osterrieder N. Equine herpesvirus type 1 devoid of gM and GP2 is severely impaired in virus egress but not direct cell-to-cell spread. Virology 2002; 293:356–367 [View Article]
    [Google Scholar]
  48. van der Meulen K, Vercauteren G, Nauwynck H, Pensaert M. A local epidemic of equine herpesvirus 1-induced neurological disorders in Belgium. Vlaams Diergeneeskundig Tijdschrift 2003; 72:366–372
    [Google Scholar]
  49. Muylle S, Simoens P, Lauwers H. Ageing horses by an examination of their incisor teeth: an (im)possible task?. Vet Rec 1996; 138:295–301 [View Article]
    [Google Scholar]
  50. Quintana AM, Landolt GA, Annis KM, Hussey GS. Immunological characterization of the equine airway epithelium and of a primary equine airway epithelial cell culture model. Vet Immunol Immunopathol 2011; 140:226–236 [View Article]
    [Google Scholar]
  51. Verbsky JW, Chatila TA. Chapter 23 - Immune Dysregulation Leading to Chronic Autoimmunity. Sullivan KE, Stiehm ER. (editors) Stiehm's Immune Deficiencies. Amsterdam: Academic Press; 2014 pp 497–516
  52. Geginat J, Sallusto F, Lanzavecchia A. Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+ ) T cells. J Exp Med 2001; 194:1711–1720 [View Article]
    [Google Scholar]
  53. Van Cleemput J, Poelaert KCK, Laval K, Maes R, Hussey GS et al. Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions. Sci Rep 2017; 7:16656 [View Article]
    [Google Scholar]
  54. Hansen JE, Lund O, Engelbrecht J, Bohr H, Nielsen JO et al. Prediction of O-glycosylation of mammalian proteins: specificity patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase. Biochem J 1995; 308:801–813 [View Article]
    [Google Scholar]
  55. Wellington JE, Allen GP, Gooley AA, Love DN, Packer NH et al. The highly O-glycosylated glycoprotein GP2 of equine herpesvirus 1 is encoded by gene 71. J Virol 1996; 70:8195–8198
    [Google Scholar]
  56. Bryant NA, Davis-Poynter N, Vanderplasschen A, Alcami A. Glycoprotein G isoforms from some alphaherpesviruses function as broad-spectrum chemokine binding proteins. Embo J 2003; 22:833–846 [View Article]
    [Google Scholar]
  57. Colle CF, O'Callaghan DJ. Transcriptional analyses of the unique short segment of EHV-1 strain Kentucky a. Virus Genes 1995; 9:257–268 [View Article]
    [Google Scholar]
  58. Thormann N, Van de Walle GR, Azab W, Osterrieder N. The role of secreted glycoprotein G of equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) in immune modulation and virulence. Virus Res 2012; 169:203–211 [View Article]
    [Google Scholar]
  59. Aubert M, Yoon M, Sloan DD, Spear PG, Jerome KR. The virological synapse facilitates herpes simplex virus entry into T cells. J Virol 2009; 83:6171–6183 [View Article]
    [Google Scholar]
  60. Schaap A, Fortin J-F, Sommer M, Zerboni L, Stamatis S et al. T-Cell tropism and the role of ORF66 protein in pathogenesis of varicella-zoster virus infection. J Virol 2005; 79:12921–12933 [View Article]
    [Google Scholar]
  61. Müller M, Carter S, Hofer MJ, Campbell IL. Review: The chemokine receptor CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in neuroimmunity--a tale of conflict and conundrum. Neuropathol Appl Neurobiol 2010; 36:368–387 [View Article]
    [Google Scholar]
  62. Huang W, Hu K, Luo S, Zhang M, Li C et al. Herpes simplex virus type 2 infection of human epithelial cells induces CXCL9 expression and CD4+ T cell migration via activation of p38-CCAAT/enhancer-binding protein-β pathway. J Immunol 2012; 188:6247–6257 [View Article]
    [Google Scholar]
  63. Molesworth-Kenyon SJ, Milam A, Rockette A, Troupe A, Oakes JE et al. Expression, inducers and cellular sources of the chemokine Mig (CXCL 9), during primary herpes simplex virus type-1 infection of the cornea. Curr Eye Res 2015; 40:800–808 [View Article]
    [Google Scholar]
  64. Viejo-Borbolla A, Muñoz A, Tabarés E, Alcamí A. Glycoprotein G from pseudorabies virus binds to chemokines with high affinity and inhibits their function. J Gen Virol 2010; 91:23–31 [View Article]
    [Google Scholar]
  65. Goodman LB, Loregian A, Perkins GA, Nugent J, Buckles EL et al. A point mutation in a herpesvirus polymerase determines neuropathogenicity. PLoS Pathog 2007; 3:e160 [View Article]
    [Google Scholar]
  66. Iversen MB, Reinert LS, Thomsen MK, Bagdonaite I, Nandakumar R et al. An innate antiviral pathway acting before interferons at epithelial surfaces. Nat Immunol 2016; 17:150–158 [View Article]
    [Google Scholar]
  67. Kobata A. Structures and functions of the sugar chains of glycoproteins. European Journal of Biochemistry 1992; 209:483–501 [View Article]
    [Google Scholar]
  68. Hart GW, Kreppel LK, Comer FI, Arnold CS, Snow DM et al. O-Glcnacylation of key nuclear and cytoskeletal proteins: reciprocity with O-phosphorylation and putative roles in protein multimerization. Glycobiology 1996; 6:711–716 [View Article]
    [Google Scholar]
  69. Wimer CL, Damiani A, Osterrieder N, Wagner B. Equine herpesvirus type-1 modulates CCL2, CCL3, CCL5, CXCL9, and CXCL10 chemokine expression. Vet Immunol Immunopathol 2011; 140:266–274 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001317
Loading
/content/journal/jgv/10.1099/jgv.0.001317
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error