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Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8+ T Cells


Epstein-Barr virus (EBV) is carried by most humans. It can cause several types of cancer. In healthy infected people, EBV persists for life in a "latent" state in white blood cells called B cells. For infected persons to remain healthy, it is crucial that they harbor CD8-positive "killer" T cells that recognize and destroy precancerous EBV-infected cells. However, this protection is imperfect, because the virus is not eliminated from the body, and the danger of EBV-associated cancer remains. How does the virus counteract CD8+ T cell control? Here we study the effects of latent membrane protein 2A (LMP2A), which is an important viral molecule because it is present in several types of EBV-associated cancers, and in latently infected cells in healthy people. We show that LMP2A counteracts the recognition of EBV-infected B cells by antiviral killer cells. We found a number of mechanisms that are relevant to this effect. Notably, LMP2A disturbs expression of molecules on B cells that interact with NKG2D, a molecule on the surface of CD8+ T cells that aids their activation. In this way, LMP2A weakens important immune responses against EBV. Similar mechanisms may operate in different types of LMP2A-expressing cancers caused by EBV.


Vyšlo v časopise: Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8+ T Cells. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004906
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004906

Souhrn

Epstein-Barr virus (EBV) is carried by most humans. It can cause several types of cancer. In healthy infected people, EBV persists for life in a "latent" state in white blood cells called B cells. For infected persons to remain healthy, it is crucial that they harbor CD8-positive "killer" T cells that recognize and destroy precancerous EBV-infected cells. However, this protection is imperfect, because the virus is not eliminated from the body, and the danger of EBV-associated cancer remains. How does the virus counteract CD8+ T cell control? Here we study the effects of latent membrane protein 2A (LMP2A), which is an important viral molecule because it is present in several types of EBV-associated cancers, and in latently infected cells in healthy people. We show that LMP2A counteracts the recognition of EBV-infected B cells by antiviral killer cells. We found a number of mechanisms that are relevant to this effect. Notably, LMP2A disturbs expression of molecules on B cells that interact with NKG2D, a molecule on the surface of CD8+ T cells that aids their activation. In this way, LMP2A weakens important immune responses against EBV. Similar mechanisms may operate in different types of LMP2A-expressing cancers caused by EBV.


Zdroje

1. Thorley-Lawson DA, Hawkins JB, Tracy SI, Shapiro M (2013) The pathogenesis of Epstein-Barr virus persistent infection. Curr Opin Virol 3: 227–232. doi: 10.1016/j.coviro.2013.04.005 23683686

2. Hislop AD, Taylor GS, Sauce D, Rickinson AB (2007) Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. Annu Rev Immunol 25: 587–617. 17378764

3. Rickinson AB (2014) Co-infections, inflammation and oncogenesis: Future directions for EBV research. Semin Cancer Biol

4. Young LS, Rickinson AB (2004) Epstein-Barr virus: 40 years on. Nat Rev Cancer 4: 757–768. 15510157

5. Moosmann A, Bigalke I, Tischer J, Schirrmann L, Kasten J et al. (2010) Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood 115: 2960–2970. doi: 10.1182/blood-2009-08-236356 20103780

6. Moosmann A, Hammerschmidt W, Kolb HJ (2012) Virus-specific T cells for therapy—approaches, problems, solutions. Eur J Cell Biol 91: 97–101. doi: 10.1016/j.ejcb.2011.04.001 21640430

7. Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW et al. (1998) Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 92: 1549–1555. 9716582

8. Hochberg D, Middeldorp JM, Catalina M, Sullivan JL, Luzuriaga K et al. (2004) Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo. Proc Natl Acad Sci U S A 101: 239–244. 14688409

9. Kuppers R (2003) B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol 3: 801–812. 14523386

10. Thorley-Lawson DA, Gross A (2004) Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med 350: 1328–1337. 15044644

11. Hislop AD, Ressing ME, van Leeuwen D, Pudney VA, Horst D et al. (2007) A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. J Exp Med 204: 1863–1873. 17620360

12. Zuo J, Currin A, Griffin BD, Shannon-Lowe C, Thomas WA et al. (2009) The Epstein-Barr virus G-protein-coupled receptor contributes to immune evasion by targeting MHC class I molecules for degradation. PLoS Pathog 5: e1000255. doi: 10.1371/journal.ppat.1000255 19119421

13. Zuo J, Thomas W, van Leeuwen D, Middeldorp JM, Wiertz EJ et al. (2008) The DNase of gammaherpesviruses impairs recognition by virus-specific CD8+ T cells through an additional host shutoff function. J Virol 82: 2385–2393. 18094150

14. Brink AA, Dukers DF, van den Brule AJ, Oudejans JJ, Middeldorp JM et al. (1997) Presence of Epstein-Barr virus latency type III at the single cell level in post-transplantation lymphoproliferative disorders and AIDS related lymphomas. J Clin Pathol 50: 911–918. 9462239

15. Blake N, Lee S, Redchenko I, Thomas W, Steven N et al. (1997) Human CD8+ T cell responses to EBV EBNA1: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing. Immunity 7: 791–802. 9430224

16. Levitskaya J, Coram M, Levitsky V, Imreh S, Steigerwald-Mullen PM et al. (1995) Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature 375: 685–688. 7540727

17. Levitskaya J, Sharipo A, Leonchiks A, Ciechanover A, Masucci MG (1997) 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 U S A 94: 12616–12621. 9356498

18. Apcher S, Komarova A, Daskalogianni C, Yin Y, Malbert-Colas L et al. (2009) mRNA translation regulation by the Gly-Ala repeat of Epstein-Barr virus nuclear antigen 1. J Virol 83: 1289–1298. doi: 10.1128/JVI.01369-08 19019958

19. Tellam J, Smith C, Rist M, Webb N, Cooper L et al. (2008) Regulation of protein translation through mRNA structure influences MHC class I loading and T cell recognition. Proc Natl Acad Sci U S A 105: 9319–9324. doi: 10.1073/pnas.0801968105 18591662

20. Yin Y, Manoury B, Fahraeus R (2003) Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1. Science 301: 1371–1374. 12958359

21. Smith C, Wakisaka N, Crough T, Peet J, Yoshizaki T et al. (2009) Discerning regulation of cis- and trans-presentation of CD8+ T-cell epitopes by EBV-encoded oncogene LMP-1 through self-aggregation. Blood 113: 6148–6152. doi: 10.1182/blood-2009-02-203687 19372256

22. Alber G, Kim KM, Weiser P, Riesterer C, Carsetti R et al. (1993) Molecular mimicry of the antigen receptor signalling motif by transmembrane proteins of the Epstein-Barr virus and the bovine leukaemia virus. Curr Biol 3: 333–339. 15335726

23. Beaufils P, Choquet D, Mamoun RZ, Malissen B (1993) The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events. EMBO J 12: 5105–5112. 8262054

24. Caldwell RG, Wilson JB, Anderson SJ, Longnecker R (1998) Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9: 405–411. 9768760

25. Mancao C, Hammerschmidt W (2007) Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood 110: 3715–3721. 17682125

26. Miller CL, Burkhardt AL, Lee JH, Stealey B, Longnecker R et al. (1995) Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity 2: 155–166. 7895172

27. Miller CL, Lee JH, Kieff E, Burkhardt AL, Bolen JB et al. (1994) Epstein-Barr virus protein LMP2A regulates reactivation from latency by negatively regulating tyrosine kinases involved in sIg-mediated signal transduction. Infect Agents Dis 3: 128–136. 7812651

28. Miller CL, Lee JH, Kieff E, Longnecker R (1994) An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking. Proc Natl Acad Sci U S A 91: 772–776. 8290598

29. Brielmeier M, Mautner J, Laux G, Hammerschmidt W (1996) The latent membrane protein 2 gene of Epstein-Barr virus is important for efficient B cell immortalization. J Gen Virol 77: 2807–2818. 8922475

30. Konishi K, Maruo S, Kato H, Takada K (2001) Role of Epstein-Barr virus-encoded latent membrane protein 2A on virus-induced immortalization and virus activation. J Gen Virol 82: 1451–1456. 11369890

31. Longnecker R, Miller CL, Miao XQ, Marchini A, Kieff E (1992) The only domain which distinguishes Epstein-Barr virus latent membrane protein 2A (LMP2A) from LMP2B is dispensable for lymphocyte infection and growth transformation in vitro; LMP2A is therefore nonessential. J Virol 66: 6461–6469. 1328675

32. Longnecker R, Miller CL, Miao XQ, Tomkinson B, Kieff E (1993) The last seven transmembrane and carboxy-terminal cytoplasmic domains of Epstein-Barr virus latent membrane protein 2 (LMP2) are dispensable for lymphocyte infection and growth transformation in vitro. J Virol 67: 2006–2013. 8383224

33. Longnecker R, Miller CL, Tomkinson B, Miao XQ, Kieff E (1993) Deletion of DNA encoding the first five transmembrane domains of Epstein-Barr virus latent membrane proteins 2A and 2B. J Virol 67: 5068–5074. 8392630

34. Speck P, Kline KA, Cheresh P, Longnecker R (1999) Epstein-Barr virus lacking latent membrane protein 2 immortalizes B cells with efficiency indistinguishable from that of wild-type virus. J Gen Virol 80: 2193–2203. 10466819

35. Wasil LR, Tomaszewski MJ, Hoji A, Rowe DT (2013) The effect of Epstein-Barr virus Latent Membrane Protein 2 expression on the kinetics of early B cell infection. PLoS ONE 8: e54010. doi: 10.1371/journal.pone.0054010 23308294

36. Shah KM, Stewart SE, Wei W, Woodman CB, O'Neil JD et al. (2009) The EBV-encoded latent membrane proteins, LMP2A and LMP2B, limit the actions of interferon by targeting interferon receptors for degradation. Oncogene 28: 3903–3914. doi: 10.1038/onc.2009.249 19718044

37. Portis T, Dyck P, Longnecker R (2003) Epstein-Barr Virus (EBV) LMP2A induces alterations in gene transcription similar to those observed in Reed-Sternberg cells of Hodgkin lymphoma. Blood 102: 4166–4178. 12907455

38. Incrocci R, McCormack M, Swanson-Mungerson M (2013) Epstein-Barr virus LMP2A increases IL-10 production in mitogen-stimulated primary B-cells and B-cell lymphomas. J Gen Virol 94: 1127–1133. doi: 10.1099/vir.0.049221-0 23303827

39. Delecluse HJ, Hilsendegen T, Pich D, Zeidler R, Hammerschmidt W (1998) Propagation and recovery of intact, infectious Epstein-Barr virus from prokaryotic to human cells. Proc Natl Acad Sci U S A 95: 8245–8250. 9653172

40. Middeldorp JM, Pegtel DM (2008) Multiple roles of LMP1 in Epstein-Barr virus induced immune escape. Semin Cancer Biol 18: 388–396. doi: 10.1016/j.semcancer.2008.10.004 19013244

41. Bejarano MT, Masucci MG (1998) Interleukin-10 abrogates the inhibition of Epstein-Barr virus-induced B-cell transformation by memory T-cell responses. Blood 92: 4256–4262. 9834231

42. Jochum S, Moosmann A, Lang S, Hammerschmidt W, Zeidler R (2012) The EBV immunoevasins vIL-10 and BNLF2a protect newly infected B cells from immune recognition and elimination. PLoS Pathog 8: e1002704. doi: 10.1371/journal.ppat.1002704 22615564

43. Zeidler R, Eissner G, Meissner P, Uebel S, Tampe R et al. (1997) Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Blood 90: 2390–2397. 9310490

44. Ng TH, Britton GJ, Hill EV, Verhagen J, Burton BR et al. (2013) Regulation of adaptive immunity; the role of interleukin-10. Front Immunol 4: 129. doi: 10.3389/fimmu.2013.00129 23755052

45. Stewart JP, Behm FG, Arrand JR, Rooney CM (1994) Differential expression of viral and human interleukin-10 (IL-10) by primary B cell tumors and B cell lines. Virology 200: 724–732. 8178456

46. Chaigne-Delalande B, Li FY, O'Connor GM, Lukacs MJ, Jiang P et al. (2013) Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science 341: 186–191. doi: 10.1126/science.1240094 23846901

47. Kong Y, Cao W, Xi X, Ma C, Cui L et al. (2009) The NKG2D ligand ULBP4 binds to TCRgamma9/delta2 and induces cytotoxicity to tumor cells through both TCRgammadelta and NKG2D. Blood 114: 310–317. doi: 10.1182/blood-2008-12-196287 19436053

48. Pappworth IY, Wang EC, Rowe M (2007) The switch from latent to productive infection in Epstein-Barr virus-infected B cells is associated with sensitization to NK cell killing. J Virol 81: 474–482. 17079298

49. Wiesmayr S, Webber SA, Macedo C, Popescu I, Smith L et al. (2012) Decreased NKp46 and NKG2D and elevated PD-1 are associated with altered NK-cell function in pediatric transplant patients with PTLD. Eur J Immunol 42: 541–550. doi: 10.1002/eji.201141832 22105417

50. Kim YS, Park GB, Lee HK, Song H, Choi IH et al. (2008) Cross-linking of B7-H1 on EBV-transformed B cells induces apoptosis through reactive oxygen species production, JNK signaling activation, and fasL expression. J Immunol 181: 6158–6169. 18941206

51. Haile ST, Dalal SP, Clements V, Tamada K, Ostrand-Rosenberg S (2013) Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression. J Immunol 191: 2829–2836. doi: 10.4049/jimmunol.1202777 23918985

52. Ruprecht CR, Lanzavecchia A (2006) Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur J Immunol 36: 810–816. 16541472

53. Wiesner M, Zentz C, Mayr C, Wimmer R, Hammerschmidt W et al. (2008) Conditional immortalization of human B cells by CD40 ligation. PLoS ONE 3: e1464. doi: 10.1371/journal.pone.0001464 18213373

54. Merchant M, Swart R, Katzman RB, Ikeda M, Ikeda A et al. (2001) The effects of the Epstein-Barr virus latent membrane protein 2A on B cell function. Int Rev Immunol 20: 805–835. 11913951

55. Schaadt E, Baier B, Mautner J, Bornkamm GW, Adler B (2005) Epstein-Barr virus latent membrane protein 2A mimics B-cell receptor-dependent virus reactivation. J Gen Virol 86: 551–559. 15722514

56. Pudney VA, Leese AM, Rickinson AB, Hislop AD (2005) CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. J Exp Med 201: 349–360. 15684323

57. Rowe M, Khanna R, Jacob CA, Argaet V, Kelly A et al. (1995) Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression. Eur J Immunol 25: 1374–1384. 7774641

58. Dukers DF, Meij P, Vervoort MB, Vos W, Scheper RJ et al. (2000) Direct immunosuppressive effects of EBV-encoded latent membrane protein 1. J Immunol 165: 663–670. 10878338

59. Lautscham G, Mayrhofer S, Taylor G, Haigh T, Leese A et al. (2001) Processing of a multiple membrane spanning Epstein-Barr virus protein for CD8(+) T cell recognition reveals a proteasome-dependent, transporter associated with antigen processing-independent pathway. J Exp Med 194: 1053–1068. 11602636

60. Lautscham G, Haigh T, Mayrhofer S, Taylor G, Croom-Carter D et al. (2003) Identification of a TAP-independent, immunoproteasome-dependent CD8+ T-cell epitope in Epstein-Barr virus latent membrane protein 2. J Virol 77: 2757–2761. 12552018

61. Tellam J, Connolly G, Green KJ, Miles JJ, Moss DJ et al. (2004) Endogenous presentation of CD8+ T cell epitopes from Epstein-Barr virus-encoded nuclear antigen 1. J Exp Med 199: 1421–1431. 15148340

62. Portis T, Longnecker R (2003) Epstein-Barr virus LMP2A interferes with global transcription factor regulation when expressed during B-lymphocyte development. J Virol 77: 105–114. 12477815

63. Portis T, Ikeda M, Longnecker R (2004) Epstein-Barr virus LMP2A: regulating cellular ubiquitination processes for maintenance of viral latency? Trends Immunol 25: 422–426. 15275641

64. Bell AI, Groves K, Kelly GL, Croom-Carter D, Hui E et al. (2006) Analysis of Epstein-Barr virus latent gene expression in endemic Burkitt's lymphoma and nasopharyngeal carcinoma tumour cells by using quantitative real-time PCR assays. J Gen Virol 87: 2885–2890. 16963746

65. Kuppers R (2009) The biology of Hodgkin's lymphoma. Nat Rev Cancer 9: 15–27. doi: 10.1038/nrc2542 19078975

66. Burdin N, Peronne C, Banchereau J, Rousset F (1993) Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med 177: 295–304. 8381152

67. Finke J, Ternes P, Lange W, Mertelsmann R, Dolken G (1993) Expression of interleukin 10 in B lymphocytes of different origin. Leukemia 7: 1852–1857. 7694007

68. Hsu DH, de Waal Malefyt R, Fiorentino DF, Dang MN, Vieira P et al. (1990) Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. Science 250: 830–832. 2173142

69. Swaminathan S, Hesselton R, Sullivan J, Kieff E (1993) Epstein-Barr virus recombinants with specifically mutated BCRF1 genes. J Virol 67: 7406–7413. 7693971

70. Beatty PR, Krams SM, Martinez OM (1997) Involvement of IL-10 in the autonomous growth of EBV-transformed B cell lines. J Immunol 158: 4045–4051. 9126962

71. Miyazaki I, Cheung RK, Dosch HM (1993) Viral interleukin 10 is critical for the induction of B cell growth transformation by Epstein-Barr virus. J Exp Med 178: 439–447. 8393476

72. Salek-Ardakani S, Arrand JR, Mackett M (2002) Epstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7 expression on human monocytes: implications for immune evasion by EBV. Virology 304: 342–351. 12504574

73. Duraiswamy J, Ibegbu CC, Masopust D, Miller JD, Araki K et al. (2011) Phenotype, function, and gene expression profiles of programmed death-1(hi) CD8 T cells in healthy human adults. J Immunol 186: 4200–4212. doi: 10.4049/jimmunol.1001783 21383243

74. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP et al. (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439: 682–687. 16382236

75. Gonzalez S, Lopez-Soto A, Suarez-Alvarez B, Lopez-Vazquez A, Lopez-Larrea C (2008) NKG2D ligands: key targets of the immune response. Trends Immunol 29: 397–403. doi: 10.1016/j.it.2008.04.007 18602338

76. Zhang B, Kracker S, Yasuda T, Casola S, Vanneman M et al. (2012) Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model. Cell 148: 739–751. doi: 10.1016/j.cell.2011.12.031 22341446

77. Nachmani D, Stern-Ginossar N, Sarid R, Mandelboim O (2009) Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe 5: 376–385. doi: 10.1016/j.chom.2009.03.003 19380116

78. Altmann M, Hammerschmidt W (2005) Epstein-Barr virus provides a new paradigm: a requirement for the immediate inhibition of apoptosis. PLoS Biol 3: e404. 16277553

79. Garrone P, Neidhardt EM, Garcia E, Galibert L, van Kooten C et al. (1995) Fas ligation induces apoptosis of CD40-activated human B lymphocytes. J Exp Med 182: 1265–1273. 7595197

80. Lee SP, Thomas WA, Murray RJ, Khanim F, Kaur S et al. (1993) HLA A2.1-restricted cytotoxic T cells recognizing a range of Epstein-Barr virus isolates through a defined epitope in latent membrane protein LMP2. J Virol 67: 7428–7435. 7693972

81. Saulquin X, Ibisch C, Peyrat MA, Scotet E, Hourmant M et al. (2000) A global appraisal of immunodominant CD8 T cell responses to Epstein-Barr virus and cytomegalovirus by bulk screening. Eur J Immunol 30: 2531–2539. 11009086

82. Meij P, Leen A, Rickinson AB, Verkoeijen S, Vervoort MB et al. (2002) Identification and prevalence of CD8(+) T-cell responses directed against Epstein-Barr virus-encoded latent membrane protein 1 and latent membrane protein 2. Int J Cancer 99: 93–99. 11948498

83. Hill A, Worth A, Elliott T, Rowland-Jones S, Brooks J et al. (1995) Characterization of two Epstein-Barr virus epitopes restricted by HLA-B7. Eur J Immunol 25: 18–24. 7531143

84. Bogedain C, Wolf H, Modrow S, Stuber G, Jilg W (1995) Specific cytotoxic T lymphocytes recognize the immediate-early transactivator Zta of Epstein-Barr virus. J Virol 69: 4872–4879. 7609055

85. Rickinson AB, Moss DJ (1997) Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection. Annu Rev Immunol 15: 405–431. 9143694

86. Diamond DJ, York J, Sun JY, Wright CL, Forman SJ (1997) Development of a candidate HLA A*0201 restricted peptide-based vaccine against human cytomegalovirus infection. Blood 90: 1751–1767. 9292508

87. Ameres S, Mautner J, Schlott F, Neuenhahn M, Busch DH et al. (2013) Presentation of an immunodominant immediate-early CD8+ T cell epitope resists human cytomegalovirus immunoevasion. PLoS Pathog 9: e1003383. doi: 10.1371/journal.ppat.1003383 23717207

88. Khan N, Cobbold M, Keenan R, Moss PA (2002) Comparative analysis of CD8+ T cell responses against human cytomegalovirus proteins pp65 and immediate early 1 shows similarities in precursor frequency, oligoclonality, and phenotype. J Infect Dis 185: 1025–1034. 11930311

89. Braud VM, Allan DS, Wilson D, McMichael AJ (1998) TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Curr Biol 8: 1–10. 9427624

90. Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K (1998) Role of interleukin 10 in specific immunotherapy. J Clin Invest 102: 98–106. 9649562

91. Iskra S, Kalla M, Delecluse HJ, Hammerschmidt W, Moosmann A (2010) Toll-like receptor agonists synergistically increase proliferation and activation of B cells by Epstein-Barr virus. J Virol 84: 3612–3623. doi: 10.1128/JVI.01400-09 20089650

92. Liu Y, de Waal Malefyt R, Briere F, Parham C, Bridon JM et al. (1997) The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor. J Immunol 158: 604–613. 8992974

93. de Brouwer AP, van Bokhoven H, Kremer H (2006) Comparison of 12 reference genes for normalization of gene expression levels in Epstein-Barr virus-transformed lymphoblastoid cell lines and fibroblasts. Mol Diagn Ther 10: 197–204. 16771605

94. Nicholls J, Hahn P, Kremmer E, Frohlich T, Arnold GJ et al. (2004) Detection of wild type and deleted latent membrane protein 1 (LMP1) of Epstein-Barr virus in clinical biopsy material. J Virol Methods 116: 79–88. 14715310

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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