1887

Abstract

In common with other herpes viruses, bovine herpes virus 1 (BHV-1) induces strong virus-specific CD8 T-cell responses. However, there is a paucity of information on the antigenic specificity of the responding T-cells. The development of a system to generate virus-specific CD8 T-cell lines from BHV-1-immune cattle, employing Theileria-transformed cell lines for antigen presentation, has enabled us to address this issue. Use of this system allowed the study to screen for CD8 T-cell antigens that are efficiently presented on the surface of virus-infected cells. Screening of a panel of 16 candidate viral gene products with CD8 T-cell lines from 3 BHV-1-immune cattle of defined MHC genotypes identified 4 antigens, including 3 immediate early (IE) gene products (ICP4, ICP22 and Circ) and a tegument protein (UL49). Identification of the MHC restriction specificities revealed that the antigens were presented by two or three class I MHC alleles in each animal. Six CD8 T-cell epitopes were identified in the three IE proteins by screening of synthetic peptides. Use of an algorithm (NetMHCpan) that predicts the peptide-binding characteristics of restricting MHC alleles confirmed and, in some cases refined, the identity of the epitopes. Analyses of the epitope specificity of the CD8 T-cell lines showed that a large component of the response is directed against these IE epitopes. The results indicate that these IE gene products are dominant targets of the CD8 T-cell response in BHV-I-immune cattle and hence are prime-candidate antigens for the generation of a subunit vaccine.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000823
2017-07-03
2019-10-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/7/1843.html?itemId=/content/journal/jgv/10.1099/jgv.0.000823&mimeType=html&fmt=ahah

References

  1. Liu T, Khanna KM, Chen X, Fink DJ, Hendricks RL. CD8+ T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons. J Exp Med 2000;191:1459–1466 [CrossRef][PubMed]
    [Google Scholar]
  2. Divito S, Cherpes TL, Hendricks RL. A triple entente: virus, neurons, and CD8+ T cells maintain HSV-1 latency. Immunol Res 2006;36:119–126 [CrossRef][PubMed]
    [Google Scholar]
  3. Burrows SR, Moss DJ, Khanna R. Understanding human T-cell-mediated immunoregulation through herpesviruses. Immunol Cell Biol 2011;89:352–358 [CrossRef][PubMed]
    [Google Scholar]
  4. Verweij MC, Horst D, Griffin BD, Luteijn RD, Davison AJ et al. Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution. PLoS Pathog 2015;11:e1004743 [CrossRef][PubMed]
    [Google Scholar]
  5. Banks TA, Allen EM, Dasgupta S, Sandri-Goldin R, Rouse BT. Herpes simplex virus type 1-specific cytotoxic T lymphocytes recognize immediate-early protein ICP27. J Virol 1991;65:3185–3191[PubMed]
    [Google Scholar]
  6. Steven NM, Annels NE, Kumar A, Leese AM, Kurilla MG et al. Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus–induced cytotoxic T cell response. J Exp Med 1997;185:1605–1618 [CrossRef][PubMed]
    [Google Scholar]
  7. Elkington R, Walker S, Crough T, Menzies M, Tellam J et al. Ex vivo profiling of CD8+-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers. J Virol 2003;77:5226–5240 [CrossRef][PubMed]
    [Google Scholar]
  8. Jing L, Haas J, Chong TM, Bruckner JJ, Dann GC et al. Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine. J Clin Invest 2012;122:654–673 [CrossRef][PubMed]
    [Google Scholar]
  9. Khanna R, Burrows SR. Role of cytotoxic T lymphocytes in Epstein-Barr virus-associated diseases. Annu Rev Microbiol 2000;54:19–48 [CrossRef][PubMed]
    [Google Scholar]
  10. Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med 2005;202:673–685 [CrossRef][PubMed]
    [Google Scholar]
  11. Hosken N, Mcgowan P, Meier A, Koelle DM, Sleath P et al. Diversity of the CD8+ T-cell response to herpes simplex virus type 2 proteins among persons with genital herpes. J Virol 2006;80:5509–5515 [CrossRef][PubMed]
    [Google Scholar]
  12. Laing KJ, Dong L, Sidney J, Sette A, Koelle DM. Immunology in the Clinic Review Series; focus on host responses: T cell responses to herpes simplex viruses. Clin Exp Immunol 2012;167:47–58 [CrossRef][PubMed]
    [Google Scholar]
  13. Jackson SE, Mason GM, Okecha G, Sissons JG, Wills MR. Diverse specificities, phenotypes, and antiviral activities of cytomegalovirus-specific CD8+ T cells. J Virol 2014;88:10894–10908 [CrossRef][PubMed]
    [Google Scholar]
  14. Wyler R, Engels M, Schwyzer M. Infectious bovine rhinotracheitis/vulvovaginitis (BHV-1). In Wittman G. (editor) Herpesvirus Diseases of Cattle, Horses and Pigs. Dev Vet Virol Boston: Kluwer Academic; 1989; pp.1–72
  15. Henderson G, Zhang Y, Jones C. The bovine herpesvirus 1 gene encoding infected cell protein 0 (bICP0) can inhibit interferon-dependent transcription in the absence of other viral genes. J Gen Virol 2005;86:2697–2702 [CrossRef][PubMed]
    [Google Scholar]
  16. Lipińska AD, Koppers-Lalic D, Rychłowski M, Admiraal P, Rijsewijk FA et al. Bovine herpesvirus 1 UL49.5 protein inhibits the transporter associated with antigen processing despite complex formation with glycoprotein M. J Virol 2006;80:5822–5832 [CrossRef][PubMed]
    [Google Scholar]
  17. 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 [CrossRef][PubMed]
    [Google Scholar]
  18. Jones C, Chowdhury S. A review of the biology of bovine herpesvirus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex and development of improved vaccines. Anim Health Res Rev 2007;8:187–205 [CrossRef][PubMed]
    [Google Scholar]
  19. Levings RL, Roth JA. Immunity to bovine herpesvirus 1: II. Adaptive immunity and vaccinology. Anim Health Res Rev 2013;14:103–123 [CrossRef][PubMed]
    [Google Scholar]
  20. van Oirschot JT. Diva vaccines that reduce virus transmission. J Biotechnol 1999;73:195–205 [CrossRef][PubMed]
    [Google Scholar]
  21. Kaashoek MJ, Rijsewijk FA, Ruuls RC, Keil GM, Thiry E et al. Virulence, immunogenicity and reactivation of bovine herpesvirus 1 mutants with a deletion in the gC, gG, gI, gE, or in both the gI and gE gene. Vaccine 1998;16:802–809 [CrossRef][PubMed]
    [Google Scholar]
  22. Campos M, Rossi CR. In vitro induction of cytotoxic lymphocytes from infectious bovine rhinotracheitis virus hyperimmune cattle. Am J Vet Res 1986;47:2411–2414[PubMed]
    [Google Scholar]
  23. Splitter GA, Eskra L, Abruzzini AF. Cloned bovine cytolytic T cells recognize bovine herpes virus-1 in a genetically restricted, antigen-specific manner. Immunology 1988;63:145–150[PubMed]
    [Google Scholar]
  24. Denis M, Slaoui M, Keil G, Babiuk LA, Ernst E et al. Identification of different target glycoproteins for bovine herpes virus type 1-specific cytotoxic T lymphocytes depending on the method of in vitro stimulation. Immunology 1993;78:7–13[PubMed]
    [Google Scholar]
  25. Hart J, Machugh ND, Morrison WI. Theileria annulata-transformed cell lines are efficient antigen-presenting cells for in vitro analysis of CD8 T cell responses to bovine herpesvirus-1. Vet Res 2011;42:119 [CrossRef][PubMed]
    [Google Scholar]
  26. Ellis SA, Hammond JA. The functional significance of cattle major histocompatibility complex class I genetic diversity. Annu Rev Anim Biosci 2014;2:285–306 [CrossRef][PubMed]
    [Google Scholar]
  27. Codner GF, Stear MJ, Reeve R, Matthews L, Ellis SA. Selective forces shaping diversity in the class I region of the major histocompatibility complex in dairy cattle. Anim Genet 2012;43:239–249 [CrossRef][PubMed]
    [Google Scholar]
  28. Hoof I, Peters B, Sidney J, Pedersen LE, Sette A et al. NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics 2009;61:1–13 [CrossRef][PubMed]
    [Google Scholar]
  29. Hansen AM, Rasmussen M, Svitek N, Harndahl M, Golde WT et al. Characterization of binding specificities of bovine leucocyte class I molecules: impacts for rational epitope discovery. Immunogenetics 2014;66:705–718 [CrossRef][PubMed]
    [Google Scholar]
  30. Pandya M, Rasmussen M, Hansen A, Nielsen M, Buus S et al. A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules. Immunogenetics 2015;67:691–703 [CrossRef][PubMed]
    [Google Scholar]
  31. Nene V, Svitek N, Toye P, Golde WT, Barlow J et al. Designing bovine T cell vaccines via reverse immunology. Ticks Tick Borne Dis 2012;3:188–192 [CrossRef][PubMed]
    [Google Scholar]
  32. Svitek N, Hansen AM, Steinaa L, Saya R, Awino E et al. Use of "one-pot, mix-and-read" peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle. Vet Res 2014;45:50 [CrossRef][PubMed]
    [Google Scholar]
  33. Hutchings DL, van Drunen Littel-van den Hurk S, Babiuk LA. Lymphocyte proliferative responses to separated bovine herpesvirus 1 proteins in immune cattle. J Virol 1990;64:5114–5122[PubMed]
    [Google Scholar]
  34. van Drunen Littel-van den Hurk S, Babiuk LA. Polypeptide specificity of the antibody response after primary and recurrent infection with bovine herpesvirus 1. J Clin Microbiol 1986;23:274–282[PubMed]
    [Google Scholar]
  35. Huang Y, Babiuk LA, van Drunen Littel-van den Hurk S. Immunization with a bovine herpesvirus 1 glycoprotein B DNA vaccine induces cytotoxic T-lymphocyte responses in mice and cattle. J Gen Virol 2005;86:887–898 [CrossRef][PubMed]
    [Google Scholar]
  36. Clevers H, Machugh ND, Bensaid A, Dunlap S, Baldwin CL et al. Identification of a bovine surface antigen uniquely expressed on CD4CD8 T cell receptor γ/δ+ T lymphocytes. Eur J Immunol 1990;20:809–817[CrossRef]
    [Google Scholar]
  37. Storset AK, Kulberg S, Berg I, Boysen P, Hope JC et al. NKp46 defines a subset of bovine leukocytes with natural killer cell characteristics. Eur J Immunol 2004;34:669–676 [CrossRef][PubMed]
    [Google Scholar]
  38. Wirth UV, Fraefel C, Vogt B, Vlcek C, Paces V et al. Immediate-early RNA 2.9 and early RNA 2.6 of bovine herpesvirus 1 are 3' coterminal and encode a putative zinc finger transactivator protein. J Virol 1992;66:2763–2772[PubMed]
    [Google Scholar]
  39. Fraefel C, Ackermann M, Schwyzer M. Identification of the bovine herpesvirus 1 circ protein, a myristylated and virion-associated polypeptide which is not essential for virus replication in cell culture. J Virol 1994;68:8082–8088[PubMed]
    [Google Scholar]
  40. Liang X, Chow B, Li Y, Raggo C, Yoo D et al. Characterization of bovine herpesvirus 1 UL49 homolog gene and product: bovine herpesvirus 1 UL49 homolog is dispensable for virus growth. J Virol 1995;69:3863–3867[PubMed]
    [Google Scholar]
  41. Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 2007;204:2473–2485 [CrossRef][PubMed]
    [Google Scholar]
  42. Yewdell JW. Confronting complexity: real-world immunodominance in antiviral CD8+ T cell responses. Immunity 2006;25:533–543 [CrossRef][PubMed]
    [Google Scholar]
  43. Tigges MA, Koelle D, Hartog K, Sekulovich RE, Corey L et al. Human CD8+ herpes simplex virus-specific cytotoxic T-lymphocyte clones recognize diverse virion protein antigens. J Virol 1992;66:1622–1634[PubMed]
    [Google Scholar]
  44. Levitskaya J, Sharipo A, Leonchiks A, Ciechanover A, Masucci MG. Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein–Barr virus nuclear antigen 1. Proc Natl Acad Sci USA 1997;94:12616–12621 [CrossRef][PubMed]
    [Google Scholar]
  45. Blake N, Lee S, Redchenko I, Thomas W, Steven N et al. Human CD8+ T cell responses to EBV EBNA1: HLA class I presentation of the (Gly-Ala)–containing protein requires exogenous processing. Immunity 1997;7:791–802 [CrossRef][PubMed]
    [Google Scholar]
  46. Silins SL, Cross SM, Elliott SL, Pye SJ, Burrows SR et al. Development of Epstein-Barr virus-specific memory T cell receptor clonotypes in acute infectious mononucleosis. J Exp Med 1996;184:1815–1824 [CrossRef][PubMed]
    [Google Scholar]
  47. Callan MF, Tan L, Annels N, Ogg GS, Wilson JD et al. Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus in vivo. J Exp Med 1998;187:1395–1402 [CrossRef][PubMed]
    [Google Scholar]
  48. Steven NM, Leese AM, Annels NE, Lee SP, Rickinson AB. Epitope focusing in the primary cytotoxic T cell response to Epstein-Barr virus and its relationship to T cell memory. J Exp Med 1996;184:1801–1813 [CrossRef][PubMed]
    [Google Scholar]
  49. Ellis SA, Morrison WI, MacHugh ND, Birch J, Burrells A et al. Serological and molecular diversity in the cattle MHC class I region. Immunogenetics 2005;57:601–606 [CrossRef][PubMed]
    [Google Scholar]
  50. Ellis SA, Holmes EC, Staines KA, Smith KB, Stear MJ et al. Variation in the number of expressed MHC genes in different cattle class I haplotypes. Immunogenetics 1999;50:319–328 [CrossRef][PubMed]
    [Google Scholar]
  51. Brown CG, Stagg DA, Purnell RE, Kanhai GK, Payne RC et al. Letter: Infection and transformation of bovine lymphoid cells in vitro by infective particles of Theileria parva. Nature 1973;245:101–103 [CrossRef][PubMed]
    [Google Scholar]
  52. Lotte Hansen L, Justesen J. PCR amplification of highly GC-rich regions. CSH Protoc 2006;2006:pdb.prot4093 [CrossRef][PubMed]
    [Google Scholar]
  53. MacHugh ND, Weir W, Burrells A, Lizundia R, Graham SP et al. Extensive polymorphism and evidence of immune selection in a highly dominant antigen recognized by bovine CD8 T cells specific for Theileria annulata. Infect Immun 2011;79:2059–2069 [CrossRef][PubMed]
    [Google Scholar]
  54. Nielsen M, Andreatta M. NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets. Genome Med 2016;8:33 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000823
Loading
/content/journal/jgv/10.1099/jgv.0.000823
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Most Cited This Month

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