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Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

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Epstein Barr Virus Volume 2

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 391))

Abstract

Epstein-Barr virus (EBV) is widely distributed in the world and associated with a still increasing number of acute, chronic, malignant and autoimmune disease syndromes. Humoral immune responses to EBV have been studied for diagnostic, pathogenic and protective (vaccine) purposes. These studies use a range of methodologies, from cell-based immunofluorescence testing to antibody-diversity analysis using immunoblot and epitope analysis using recombinant or synthetic peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D), EA(R) and EBNA) are defined at cellular and molecular levels, providing a historic overview. The characteristic antibody responses to these complexes in health and disease are described, and differences are highlighted by clinical examples. Options for EBV vaccination are briefly addressed. For a selected number of immunodominant proteins, in particular EBNA1, the interaction with human antibodies is further detailed at the epitope level, revealing interesting insights for structure, function and immunological aspects, not considered previously. Humoral immune responses against EBV-encoded tumour antigens LMP1, LMP2 and BARF1 are addressed, which provide novel options for targeted immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are given, and mechanisms of antigen mimicry are briefly discussed. Further analysis of humoral immune responses against EBV in health and disease in carefully selected patient cohorts will open new options for understanding pathogenesis of individual EBV-linked diseases and developing targeted diagnostic and therapeutic approaches.

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References

  • Ambinder RF, Mullen MA, Chang YN, Hayward GS, Hayward SD (1991) Functional domains of Epstein-Barr virus nuclear antigen EBNA-1. J Virol 65(3):1466–1478

    PubMed Central  CAS  PubMed  Google Scholar 

  • Asito AS, Piriou E, Odada PS, Fiore N, Middeldorp JM, Long C, Dutta S, Lanar DE, Jura WG, Ouma C, Otieno JA, Moormann AM, Rochford R (2010) Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt’s lymphoma patients: a case control study. Infect Agent Cancer 5:13. doi:10.1186/1750-9378-5-13

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, Hatfull G, Hudson GS, Satchwell SC, Séguin C, Tuffnell PS, Barrell BG (1984) DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310(5974):207–211

    Article  CAS  PubMed  Google Scholar 

  • Balandraud N, Roudier J, Roudier C (2004) Epstein-Barr virus and rheumatoid arthritis. Autoimmun Rev 3(5):362–367

    Article  CAS  PubMed  Google Scholar 

  • Bauer G (2001) Simplicity through complexity: immunoblot with recombinant antigens as the new gold standard in Epstein-Barr virus serology. Clin Lab 47(5–6):223–230

    CAS  PubMed  Google Scholar 

  • Bayliss GJ, Deby G, Wolf H (1983) An immunoprecipitation blocking assay for the analysis of EBV induced antigens. J Virol Methods 7(4):229–239

    Article  CAS  PubMed  Google Scholar 

  • Bochkarev A, Bochkareva E, Frappier L, Edwards AM (1998) The 2.2 A structure of a permanganate-sensitive DNA site bound by the Epstein-Barr virus origin binding protein, EBNA1. J Mol Biol 284(5):1273–1278

    Article  CAS  PubMed  Google Scholar 

  • Bravo D, Muñoz-Cobo B, Costa E, Clari MA, Tormo N, Navarro D (2009) Evaluation of an immunofiltration assay that detects immunoglobulin M antibodies against the ZEBRA protein for the diagnosis of Epstein-Barr virus infectious mononucleosis in immunocompetent patients. Clin Vaccine Immunol 16(6):885–888. doi:10.1128/CVI.00123-09

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cacioppo JT, Kiecolt-Glaser JK, Malarkey WB, Laskowski BF, Rozlog LA, Poehlmann KM, Burleson MH, Glaser R (2002) Autonomic and glucocorticoid associations with the steady-state expression of latent Epstein-Barr virus. Horm Behav 42(1):32–41

    Article  CAS  PubMed  Google Scholar 

  • Cameron B, Flamand L, Juwana H, Middeldorp J, Naing Z, Rawlinson W, Ablashi D (2010) Lloyd A (2012) Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome. J Med Virol 82(10):1684–1688. doi:10.1002/jmv.21873

    Article  CAS  PubMed  Google Scholar 

  • Chen MR, Middeldorp JM, Hayward SD (1993) Separation of the complex DNA binding domain of EBNA-1 into DNA recognition and dimerization subdomains of novel structure. J Virol 67(8):4875–4885

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chen R, Zhang D, Mao Y, Zhu J, Ming H, Wen J, Ma J, Cao Q, Lin H, Tang Q, Liang J, Feng Z (2012) A human Fab-based immunoconjugate specific for the LMP1 extracellular domain inhibits nasopharyngeal carcinoma growth in vitro and in vivo. Mol Cancer Ther 11(3):594–603. doi:10.1158/1535-7163.MCT-11-0725

    Article  CAS  PubMed  Google Scholar 

  • Cheng YC, Chen JY, Glaser R, Henle W (1980) Frequency and levels of antibodies to Epstein-Barr virus-specific DNAs are elevated in patients with nasopharyngeal carcinoma. Proc Natl Acad Sci USA. 77(10):6162–6165

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cheng WM, Chan KH, Chen HL, Luo RX, Ng SP, Luk W, Zheng BJ, Ji MF, Liang JS, Sham JS, Wang DK, Zong YS, Ng MH (2002) Assessing the risk of nasopharyngeal carcinoma on the basis of EBV antibody spectrum. Int J Cancer 97(4):489–492

    Article  CAS  PubMed  Google Scholar 

  • Cho MS, Milman G, Hayward SD (1985) A second Epstein-Barr virus early antigen gene in BamHI fragment M encodes a 48- to 50-kilodalton nuclear protein. J Virol 56(3):860–866

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cohen JI, Mocarski ES, Raab-Traub N, Corey L, Nabel GJ (2013) The need and challenges for development of an Epstein-Barr virus vaccine. Vaccine 31(Suppl 2):B194–B196. doi:10.1016/j.vaccine.2012.09.041

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cornaby C, Gibbons L, Mayhew V, Sloan CS, Welling A, Poole BD (2014) B cell epitope spreading: mechanisms and contribution to autoimmune diseases. Immunol Lett 163(1):56–68. doi:10.1016/j.imlet.2014.11.001

    Article  PubMed  CAS  Google Scholar 

  • Cornillet M, Verrouil E, Cantagrel A, Serre G, Nogueira L (2015) In ACPA-positive RA patients, antibodies to EBNA35-58Cit, a citrullinated peptide from the Epstein-Barr nuclear antigen-1, strongly cross-react with the peptide β60-74Cit which bears the immunodominant epitope of citrullinated fibrin. Immunol Res 61(1–2):117–125. doi:10.1007/s12026-014-8584-2

    Article  CAS  PubMed  Google Scholar 

  • Daikoku T, Kudoh A, Fujita M, Sugaya Y, Isomura H, Shirata N, Tsurumi T (2005) Architecture of replication compartments formed during Epstein-Barr virus lytic replication. J Virol 79(6):3409–3418

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dardari R, Menezes J, Drouet E, Joab I, Benider A, Bakkali H, Kanouni L, Jouhadi H, Benjaafar N, El Gueddari B, Hassar M, Khyatti M (2008) Analyses of the prognostic significance of the Epstein-Barr virus transactivator ZEBRA protein and diagnostic value of its two synthetic peptides in nasopharyngeal carcinoma. J Clin Virol 41(2):96–103

    Article  CAS  PubMed  Google Scholar 

  • D’Arrigo I, Cló E, Bergström T, Olofsson S, Blixt O (2013) Diverse IgG serum response to novel glycopeptide epitopes detected within immunodominant stretches of Epstein-Barr virus glycoprotein 350/220: diagnostic potential of O-glycopeptide microarrays. Glycoconj J 30(7):633–640. doi:10.1007/s10719-012-9465-3

    Article  PubMed  CAS  Google Scholar 

  • de Ory F, Guisasola E, Tarragó D, Sanz JC (2014) Application of a commercial immunoblot to define EBV IgG seroprofiles. J Clin Lab Anal. doi:10.1002/jcla.21726

    PubMed  Google Scholar 

  • De Paschale M, Clerici P (2012) Serological diagnosis of Epstein-Barr virus infection: problems and solutions. World J Virol. 1(1):31–43. doi:10.5501/wjv.v1.i1.31

    Article  PubMed Central  PubMed  Google Scholar 

  • de Sanjosé S, de Sanjosé S, Bosch R, Schouten T, Verkuijlen S, Nieters A, Foretova L, Maynadié M, Cocco PL, Staines A, Becker N, Brennan P, Benavente Y, Boffetta P, Meijer CJ, Middeldorp JM et al (2007) Epstein-Barr virus infection and risk of lymphoma: immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controls. Int J Cancer 121(8):1806–1812

    Google Scholar 

  • Delbende C, Verwaerde C, Mougel A, Tranchand Bunel D (2009) Induction of therapeutic antibodies by vaccination against external loops of tumor-associated viral latent membrane protein. J Virol 83(22):11734–11745. doi:10.1128/JVI.00578-09

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dillner J, Kallin B, Ehlin-Henriksson B, Rymo L, Henle W, Henle G, Klein G (1986) The Epstein-Barr virus determined nuclear antigen is composed of at least three different antigens. Int J Cancer 37(2):195–200

    Article  CAS  PubMed  Google Scholar 

  • Draborg AH, Jørgensen JM, Müller H, Nielsen CT, Jacobsen S, Iversen LV, Theander E, Nielsen LP, Houen G, Duus K (2012) Epstein-Barr virus early antigen diffuse (EBV-EA/D)-directed immunoglobulin A antibodies in systemic lupus erythematosus patients. Scand J Rheumatol 41(4):280–289

    Article  CAS  PubMed  Google Scholar 

  • Dukers DF, Meij P, Vervoort MB, Vos W, Scheper RJ, Meijer CJ, Bloemena E, Middeldorp JM (2000) Direct immunosuppressive effects of EBV-encoded latent membrane protein 1. J Immunol 165(2):663–670

    Article  CAS  PubMed  Google Scholar 

  • Fachiroh J, Schouten T, Hariwiyanto B, Paramita DK, Harijadi A, Haryana SM, Ng MH, Middeldorp JM (2004) Molecular diversity of Epstein-Barr virus IgG and IgA antibody responses in nasopharyngeal carcinoma: a comparison of Indonesian, Chinese, and European subjects. J Infect Dis 190(1):53–62

    Article  CAS  PubMed  Google Scholar 

  • Fachiroh J, Paramita DK, Hariwiyanto B, Harijadi A, Dahlia HL, Indrasari SR, Kusumo H, Zeng YS, Schouten T, Mubarika S, Middeldorp JM (2006) Single-assay combination of Epstein-Barr Virus (EBV) EBNA1- and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients: options for field screening. J Clin Microbiol 44(4):1459–1467

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fachiroh J, Stevens SJ, Haryana SM, Middeldorp JM (2010) Combination of Epstein-Barr virus scaffold (BdRF1/VCA-p40) and small capsid protein (BFRF3/VCA-p18) into a single molecule for improved serodiagnosis of acute and malignant EBV-driven disease. J Virol Methods 169(1):79–86. doi:10.1016/j.jviromet.2010.07.001

    Article  CAS  PubMed  Google Scholar 

  • Falk K, Gratama JW, Rowe M, Zou JZ, Khanim F, Young LS, Oosterveer MA, Ernberg I (1995a) The role of repetitive DNA sequences in the size variation of Epstein-Barr virus (EBV) nuclear antigens, and the identification of different EBV isolates using RFLP and PCR analysis. J Gen Virol 76(Pt 4):779–790

    Article  CAS  PubMed  Google Scholar 

  • Falk K, Linde A, Johnson D, Lennette E, Ernberg I, Lundkvist A (1995b) Synthetic peptides deduced from the amino acid sequence of Epstein-Barr virus nuclear antigen 6 (EBNA 6): antigenic properties, production of monoreactive reagents, and analysis of antibody responses in man. J Med Virol 46(4):349–357

    Article  CAS  PubMed  Google Scholar 

  • Fattal I, Shental N, Molad Y, Gabrielli A, Pokroy-Shapira E, Oren S, Livneh A, Langevitz P, Pauzner R, Sarig O, Gafter U, Domany E, Cohen IR (2014) Epstein-Barr virus antibodies mark systemic lupus erythematosus and scleroderma patients negative for anti-DNA. Immunology 141(2):276–285. doi:10.1111/imm.12200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Finke J, Rowe M, Kallin B, Ernberg I, Rosén A, Dillner J, Klein G.(1987) Monoclonal and polyclonal antibodies against Epstein-Barr virus nuclear antigen 5 (EBNA-5) detect multiple protein species in Burkitt’s lymphoma and lymphoblastoid cell lines. J Virol 61(12):3870–3878

    Google Scholar 

  • Fox R, Sportsman R, Rhodes G, Luka J, Pearson G, Vaughan J (1986) Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen. J Clin Invest 77(5):1539–1547

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Frappier L (2012) EBNA1 and host factors in Epstein-Barr virus latent DNA replication. Curr Opin Virol 733–739. doi:10.1016/j.coviro.2012.09.005

  • Füst G (2013) The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders—Similarities and differences. Eur J Microbiol Immunol 1(4):267–278. doi:10.1556/EuJMI.1.2011.4.2

    Article  Google Scholar 

  • Gärtner BC, Hess RD, Bandt D, Kruse A, Rethwilm A, Roemer K, Mueller-Lantzsch N (2003) Evaluation of four commercially available Epstein-Barr virus enzyme immunoassays with an immunofluorescence assay as the reference method. Clin Diagn Lab Immunol 10(1):78–82

    PubMed Central  PubMed  Google Scholar 

  • Geser A, Day NE, de-Thé GB, Chew BK, Freund RJ, Kwan HC, Lavoue MF, Simkovic D, Sohier R (1974) Bull World Health Organ 50(5):389–400

    Google Scholar 

  • Glaser R, Boyd A, Stoerker J, Holliday J (1983) Functional mapping of the Epstein-Barr virus genome: identification of sites coding for the restricted early antigen, the diffuse early antigen, and the nuclear antigen. Virology 129(1):188–198

    Article  CAS  PubMed  Google Scholar 

  • Glaser R, Padgett DA, Litsky ML, Baiocchi RA, Yang EV, Chen M, Yeh PE, Klimas NG, Marshall GD, Whiteside T, Herberman R, Kiecolt-Glaser J, Williams MV (2005) Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer. Brain Behav Immunol 19(2):91–103

    Article  CAS  Google Scholar 

  • Grässer FA, Murray PG, Kremmer E, Klein K, Remberger K, Feiden W, Reynolds G, Niedobitek G, Young LS, Mueller-Lantzsch N (1994) Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin’s disease. Blood 84(11):3792–3798

    PubMed  Google Scholar 

  • Grogan E, Jenson H, Countryman J, Heston L, Gradoville L, Miller G (1987) Transfection of a rearranged viral DNA fragment, WZhet, stably converts latent Epstein-Barr viral infection to productive infection in lymphoid cells. Proc Natl Acad Sci USA 84(5):1332–1336

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Henle W, Henle GE, Horwitz CA (1974) Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Hum Pathol 5(5):551–565

    Article  CAS  PubMed  Google Scholar 

  • Henle W, Henle G, Lennette ET (1979) The Epstein-Barr virus. Sci Am 241(1):48–59

    Article  CAS  PubMed  Google Scholar 

  • Henle W, Henle G, Andersson J, Ernberg I, Klein G, Horwitz CA, Marklund G, Rymo L, Wellinder C, Straus SE (1987) Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc Natl Acad Sci USA. 84(2):570–574

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hennard C, Pfuhl T, Buettner M, Becker KF, Knöfel T, Middeldorp J, Kremmer E, Niedobitek G, Grässer F (2006) The antibody 2B4 directed against the Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) detects MAGE-4: implications for studies on the EBV association of human cancers. J Pathol 209(4):430–435

    Article  CAS  PubMed  Google Scholar 

  • Hennesy K, Kieff E (1983) One of two Epstein-Barr virus nuclear antigens contains a glycine-alanine copolymer domain. Proc Natl Acad Sci USA 80(18):5665–5669

    Article  Google Scholar 

  • Henson BW, Perkins EM, Cothran JE, Desai P (2009) Self-assembly of Epstein-Barr virus capsids. J Virol 83(8):3877–3890. doi:10.1128/JVI.01733-08

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hess RD (2003) Routine Epstein-Barr virus diagnostics from the laboratory perspective: still challenging after 35 years. J Clin Microbiol 42(8):3381–3387

    Article  Google Scholar 

  • Heston L, Rabson M, Brown N, Miller G (1982) New Epstein-Barr virus variants from cellular subclones of P3 J-HR-1 Burkitt lymphoma. Nature 295(5845):160–163

    Article  CAS  PubMed  Google Scholar 

  • Hinderer W, Lang D, Rothe M, Vornhagen R, Sonneborn HH, Wolf H (1999) Serodiagnosis of Epstein-Barr virus infection by using recombinant viral capsid antigen fragments and autologous gene fusion. J Clin Microbiol 37(10):3239–3244

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hinton HJ, Jegerlehner A, Bachmann MF (2008) Pattern recognition by B cells: the role of antigen repetitiveness versus Toll-like receptors. Curr Top Microbiol Immunol 319:1–15

    CAS  PubMed  Google Scholar 

  • Hoebe EK, Hutajulu SH, van Beek J, Stevens SJ, Paramita DK, Greijer AE, Middeldorp JM (2011) Purified hexameric Epstein-Barr virus-encoded BARF1 protein for measuring anti-BARF1 antibody responses in nasopharyngeal carcinoma patients. Clin Vaccine Immunol 18(2):298–304. doi:10.1128/CVI.00193-10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hoebe EK, Le Large TY, Greijer AE, Middeldorp JM (2013) BamHI-A rightward frame 1, an Epstein-Barr virus-encoded oncogene and immune modulator. Rev Med Virol 23(6):367–383. doi:10.1002/rmv.1758

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Horst D, Burmeister WP, Boer IG, van Leeuwen D, Buisson M, Gorbalenya AE, Wiertz EJ, Ressing ME (2012) The “Bridge” in the Epstein-Barr virus alkaline exonuclease protein BGLF5 contributes to shutoff activity during productive infection. J Virol 86(17):9175–9187. doi:10.1128/JVI.00309-12

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hu B, Hong G, Li Z, Xu J, Zhu Z, Li L (2007) Expression of VCA (viral capsid antigen) and EBNA1 (Epstein-Barr-virus-encoded nuclear antigen 1) genes of Epstein-Barr virus in Pichia pastoris and application of the products in a screening test for patients with nasopharyngeal carcinoma. Biotechnol Appl Biochem 47(Pt 1):59–69

    PubMed  Google Scholar 

  • Hussain M, Gatherer D, Wilson JB (2014) Modelling the structure of full-length Epstein-Barr virus nuclear antigen 1. Virus Genes 49(3):358–372. doi:10.1007/s11262-014-1101-9

    Article  CAS  PubMed  Google Scholar 

  • Igoe A, Scofield RH (2013) Autoimmunity and infection in Sjögren’s syndrome. Curr Opin Rheumatol 25(4):480–487. doi:10.1097/BOR.0b013e32836200d2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Iwakiri D (2014) Epstein-Barr virus-encoded RNAs: key molecules in viral pathogenesis. Cancers (Basel) 6(3):1615–1630. doi:10.3390/cancers6031615

    Article  CAS  Google Scholar 

  • Jafari N, van Nierop GP, Verjans GM, Osterhaus AD, Middeldorp JM, Hintzen RQ (2010) No evidence for intrathecal IgG synthesis to Epstein Barr virus nuclear antigen-1 in multiple sclerosis. J Clin Virol 49(1):26–31. doi:10.1016/j.jcv.2010.06.007

    Article  CAS  PubMed  Google Scholar 

  • Jaksch P, Wiedemann D, Kocher A, Muraközy G, Augustin V, Klepetko W (2013) Effect of cytomegalovirus immunoglobulin on the incidence of lymphoproliferative disease after lung transplantation: single-center experience with 1157 patients. Transplantation 95(5):766–772. doi:10.1097/TP.0b013e31827df7a7

    Article  CAS  PubMed  Google Scholar 

  • James JA, Robertson JM (2012) Lupus and Epstein-Barr. Curr Opin Rheumatol 24(4):383–388. doi:10.1097/BOR.0b013e3283535801

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jenson HB, Grant GM, Ench Y, Heard P, Thomas CA, Hilsenbeck SG, Moyer MP (1998) Immunofluorescence microscopy and flow cytometry characterization of chemical induction of latent Epstein-Barr virus. Clin Diagn Lab Immunol 5(1):91–97

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ji MF, Wang DK, Yu YL, Guo YQ, Liang JS, Cheng WM, Zong YS, Chan KH, Ng SP, Wei WI, Chua DT, Sham JS, Ng MH (2007) Sustained elevation of Epstein-Barr virus antibody levels preceding clinical onset of nasopharyngeal carcinoma. Br J Cancer 96(4):623–630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jilg W, Bogedain C, Mairhofer H, Gu SY, Wolf H (1994) The Epstein-Barr virus-encoded glycoprotein gp 110 (BALF 4) can serve as a target for antibody-dependent cell-mediated cytotoxicity (ADCC). Virology 202(2):974–977

    Article  CAS  PubMed  Google Scholar 

  • Joab I, Triki H, de Saint Martin J, Perricaudet M, Nicolas JC (1991) Detection of anti-Epstein-Barr virus trans-activator (ZEBRA) antibodies in sera from patients with human immunodeficiency virus. J Infect Dis 163(1):53–56

    Article  CAS  PubMed  Google Scholar 

  • Jones JF, Straus SE (1987) Chronic Epstein-Barr virus infection. Annu Rev Med 38:195–209

    Article  CAS  PubMed  Google Scholar 

  • Kenney S, Kamine J, Holley-Guthrie E, Lin JC, Mar EC, Pagano J (1989a) The Epstein-Barr virus (EBV) BZLF1 immediate-early gene product differentially affects latent versus productive EBV promoters. J Virol 63(4):1729–1736

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kenney S, Holley-Guthrie E, Mar EC, Smith M (1989b) The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators. J Virol 63(9):3878–3883

    PubMed Central  CAS  PubMed  Google Scholar 

  • Khyatti M, Stefanescu I, Blagdon M, Menezes J (1994) Epstein-Barr virus gp350-specific antibody titers and antibody-dependent cellular cytotoxic effector function in different groups of patients: a study using cloned gp350-expressing transfected human T cell targets. J Infect Dis 170(6):1439–1447

    Article  CAS  PubMed  Google Scholar 

  • Kim Y, Shin A, Gwack J, Ko KP, Kim CS, Park SK, Hong YC, Kang D, Yoo KY (2009) Epstein-Barr virus antibody level and gastric cancer risk in Korea: a nested case-control study. Br J Cancer 101(3):526–529

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kimura H (2006) Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev Med Virol 16(4):251–261

    Article  PubMed  Google Scholar 

  • Kishishita M, Luka J, Vroman B, Poduslo JF, Pearson GR (1984) Production of monoclonal antibody to a late intracellular Epstein-Barr virus-induced antigen. Virology 133(2):363–375

    Article  CAS  PubMed  Google Scholar 

  • Klein G, Clifford P, Henle G, Henle W, Geering G, Old LJ (1969) EBV-associated serological patterns in a Burkitt lymphoma patient during regression and recurrence. Int J Cancer 4(4):416–421

    Article  CAS  PubMed  Google Scholar 

  • Lassmann H, Niedobitek G, Aloisi F, Middeldorp JM; NeuroproMiSe EBV Working Group (2011) Epstein-Barr virus in the multiple sclerosis brain: a controversial issue. Brain 134(Pt 9):2772–2786. doi:10.1093/brain/awr197

    Google Scholar 

  • Lee SK (1999) Four consecutive arginine residues at positions 836-839 of EBV gp110 determine intracellular localization of gp110. Virology 264(2):350–358

    Article  CAS  PubMed  Google Scholar 

  • Lee SP, Brooks JM, Al-Jarrah H, Thomas WA, Haigh TA, Taylor GS, Humme S, Schepers A, Hammerschmidt W, Yates JL, Rickinson AB, Blake NW (2004) CD8 T cell recognition of endogenously expressed Epstein-Barr virus nuclear antigen 1. J Exp Med 199(10):1409–1420

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leen A, Meij P, Redchenko I, Middeldorp J, Bloemena E, Rickinson A, Blake N (2001) Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human CD4(+) T-helper 1 responses. J Virol 75(18):8649–8659

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lennette ET, Winberg G, Yadav M, Enblad G, Klein G (1995) Antibodies to LMP2A/2B in EBV-carrying malignancies. Eur J Cancer 31A(11):1875–1878

    Article  CAS  PubMed  Google Scholar 

  • Lerner AM, Ariza ME, Williams M, Jason L, Beqaj S, Fitzgerald JT, Lemeshow S (2012) Glaser R (2012) Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset. PLoS One 7(11):e47891. doi:10.1371/journal.pone.0047891

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Levin LI, Chang ET, Ambinder RF, Lennette ET, Rubertone MV, Mann RB, Borowitz M, Weir EG, Abbondanzo SL, Mueller NE (2012) Atypical pre-diagnosis Epstein-Barr virus serology restricted to EBV-positive hodgkin lymphoma. Blood 120(18):3750–3755. doi:10.1182/blood-2011-12-390823

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Levine D, Tilton RC, Parry MF, Klenk R, Morelli A, Hofreuter N (1994) False positive EBNA IgM and IgG antibody tests for infectious mononucleosis in children. Pediatrics 94(6):892–894

    CAS  PubMed  Google Scholar 

  • Levitskaya J, Coram M, Levitsky V, Imreh S, Steigerwald-Mullen PM, Klein G, Kurilla MG, Masucci MG (1985) Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature 375(6533):685–688

    Article  Google Scholar 

  • Linde A, Kallin B, Dillner J, Andersson J, Jägdahl L, Lindvall A, Wahren B (1990) Evaluation of enzyme-linked immunosorbent assays with two synthetic peptides of Epstein-Barr virus for diagnosis of infectious mononucleosis. J Infect Dis 161(5):903–909

    Article  CAS  PubMed  Google Scholar 

  • Liu MT, Hsu TY, Lin SF, Seow SV, Liu MY, Chen JY, Yang CS (1998) Distinct regions of EBV DNase are required for nuclease and DNA binding activities. Virology 242(1):6–13

    Article  CAS  PubMed  Google Scholar 

  • Long HM, Haigh TA, Gudgeon NH, Leen AM, Tsang CW, Brooks J, Landais E, Houssaint E, Lee SP, Rickinson AB, Taylor GS (2005) CD4 + T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines. J Virol 79(8):4896–4907

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lossius A, Johansen JN, Torkildsen Ø, Vartdal F, Holmøy T (2012) Epstein-Barr virus in systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis—association and causation. Viruses 4(12):3701–3730

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Luka J, Miller G, Jörnvall H, Pearson GR (1986) Characterization of the restricted component of Epstein-Barr virus early antigens as a cytoplasmic filamentous protein. J Virol 58(3):748–756

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lünemann JD, Edwards N, Muraro PA, Hayashi S, Cohen JI, Münz C, Martin R (2008) Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis. Brain 129(Pt 6):1493–506

    Google Scholar 

  • Lünemann JD, Tintoré M, Messmer B, Strowig T, Rovira A, Perkal H, Caballero E, Münz C, Montalban X, Comabella M (2010) Elevated Epstein-Barr virus-encoded nuclear antigen-1 immune responses predict conversion to multiple sclerosis. Ann Neurol 67(2):159–169. doi:10.1002/ana.21886

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mackay LK, Long HM, Brooks JM, Taylor GS, Leung CS, Chen A, Wang F, Rickinson AB (2009) T cell detection of a B-cell tropic virus infection: newly-synthesised versus mature viral proteins as antigen sources for CD4 and CD8 epitope display. PLoS Pathog 5(12):e1000699. doi:10.1371/journal.ppat.1000699

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Magalith M, Manor D, Goldblum N (1982) Organophosphorous compounds as inhibitors of EBV infection and transformation. Dev Biol Stand 52:515–526

    Google Scholar 

  • Magrath IT, Henle W (1975) Changes in antibodies to Epstein-Barr virus-associated antigens with the development of Burkitt’s lymphoma. IARC Sci Publ 11(Pt 2):275–281

    PubMed  Google Scholar 

  • Marklund G, Henle W, Henle G, Ernberg I (1986) IgA antibodies to Epstein-Barr virus in infectious mononucleosis. Scand J Infect Dis 18(2):111–119

    Google Scholar 

  • Meij P, Vervoort MB, Aarbiou J, van Dissel P, Brink A, Bloemena E, Meijer CJ, Middeldorp JM (1999) Restricted low-level human antibody responses against Epstein-Barr virus (EBV)-encoded latent membrane protein 1 in a subgroup of patients with EBV-associated diseases. J Infect Dis 179(5):1108–1115

    Article  CAS  PubMed  Google Scholar 

  • Meij P, Vervoort MB, Bloemena E, Schouten TE, Schwartz C, Grufferman S, Ambinder RF, Middeldorp JM (2002) Antibody responses to Epstein-Barr virus-encoded latent membrane protein-1 (LMP1) and expression of LMP1 in juvenile Hodgkin’s disease. J Med Virol 68(3):370–377

    Article  CAS  PubMed  Google Scholar 

  • Middeldorp JM (1993a) Epstein-Barr virus peptides and antibodies against these peptides US Patent 5843405. http://www.google.com/patents/US5843405

  • Middeldorp JM (1993b) An epitope; for a diagnostic kit. US patent 5965353 http://www.google.nl/patents/US5965353

  • Middeldorp JM (2001) Method for the identification of extracellular domains of Epstein Barr virus (EBV) tumor-associated latent membrane proteins and for the selection of antibody reagents reactive therewith. US patent 20110064759, US 8241639; Extracellular domains of Epstein Barr Virus (EBV) tumor-associated latent membrane proteins, CN1526072A. http://www.google.com.ar/patents/US8241639

  • Middeldorp JM (2002) Molecular diagnosis of viral infections in renal transplant recipients. Curr Opin Nephrol Hypertens 11(6):665–672

    Article  PubMed  Google Scholar 

  • Middeldorp JM, Herbrink P (1988) Epstein-Barr virus specific marker molecules for early diagnosis of infectious mononucleosis. J Virol Methods 21(1–4):133–146

    Article  CAS  PubMed  Google Scholar 

  • Middeldorp JM, Meloen RH (1988) Epitope-mapping on the Epstein-Barr virus major capsid protein using systematic synthesis of overlapping oligopeptides. J Virol Methods 21(1–4):147–159

    Article  CAS  PubMed  Google Scholar 

  • Miller G (1990) The switch between latency and replication of Epstein-Barr virus. J Infect Dis 161(5):833–844

    Article  CAS  PubMed  Google Scholar 

  • Miller G, Rabson M, Heston L (1984) Epstein-Barr virus with heterogeneous DNA disrupts latency. J Virol 50(1):174–182

    PubMed Central  CAS  PubMed  Google Scholar 

  • Miller G, Grogan E, Rowe D, Rooney C, Heston L, Eastman R, Andiman W, Niederman J, Lenoir G, Henle W, Henle G (1987) Selective lack of antibody to a component of EB nuclear antigen in patients with chronic active Epstein-Barr virus infection. J Infect Dis 156(1):26–35

    Article  CAS  PubMed  Google Scholar 

  • Milman G, Scott AL, Cho MS, Hartman SC, Ades DK, Hayward GS, Ki PF, August JT, Hayward SD (1985) Carboxyl-terminal domain of the Epstein-Barr virus nuclear antigen is highly immunogenic in man. Proc Natl Acad Sci USA 82(18):6300–6304

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mockridge CI, Rahman A, Buchan S, Hamblin T, Isenberg DA, Stevenson FK, Potter KN (2004) Common patterns of B cell perturbation and expanded V4-34 immunoglobulin gene usage in autoimmunity and infection. Autoimmunity 37(1):9–15

    Article  PubMed  CAS  Google Scholar 

  • Mueller N, Evans A, Harris NL, Comstock GW, Jellum E, Magnus K, Orentreich N, Polk BF, Vogelman J (1989) Hodgkin’s disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med 320(11):689–695

    Article  CAS  PubMed  Google Scholar 

  • Munger KL, Levin LI, O’Reilly EJ, Falk KI, Ascherio A (2011) Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel. Mult Scler 17(10):1185–1193. doi:10.1177/1352458511408991

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Münz C, Bickham KL, Subklewe M, Tsang ML, Chahroudi A, Kurilla MG, Zhang D, O’Donnell M, Steinman RM (2000) Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med 191(10):1649–1660

    Article  PubMed Central  PubMed  Google Scholar 

  • Paramita DK, Fachiroh J, Artama WT, van Benthem E, Haryana SM, Middeldorp JM (2007) Native early antigen of Epstein-Barr virus, a promising antigen for diagnosis of nasopharyngeal carcinoma. J Med Virol 79(11):1710–1721

    Article  CAS  PubMed  Google Scholar 

  • Paramita DK, Fachiroh J, Haryana SM, Middeldorp JM (2008) Evaluation of commercial EBV RecombLine assay for diagnosis of nasopharyngeal carcinoma. J Clin Virol 42(4):343–352. doi:10.1016/j.jcv.2008.03.006

    Article  CAS  PubMed  Google Scholar 

  • Paramita DK, Fatmawati C, Juwana H, van Schaijk FG, Fachiroh J, Haryana SM, Middeldorp JM (2011) Humoral immune responses to Epstein-Barr virus encoded tumor associated proteins and their putative extracellular domains in nasopharyngeal carcinoma patients and regional controls. J Med Virol 83(4):665–678. doi:10.1002/jmv.21960

    Article  CAS  PubMed  Google Scholar 

  • Pearson G, Dewey F, Klein G, Henle G, Henle W (1970) Relation between neutralization of Epstein-Barr virus and antibodies to cell-membrane antigens-induced by the virus. J Natl Cancer Inst 45(5):989–995

    CAS  PubMed  Google Scholar 

  • Pender MP (2011) The essential role of Epstein-Barr virus in the pathogenesis of multiple sclerosis. Neuroscientist 17(4):351–367. doi:10.1177/1073858410381531

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pither RJ, Zhang CX, Shiels C, Tarlton J, Finerty S, Morgan AJ (1992) Mapping of B-cell epitopes on the polypeptide chain of the Epstein-Barr virus major envelope glycoprotein and candidate vaccine molecule gp340. J Virol 66(2):1246–1251

    PubMed Central  CAS  PubMed  Google Scholar 

  • Polack A, Delius H, Zimber U, Bornkamm GW (1984) Two deletions in the Epstein-Barr virus genome of the Burkitt lymphoma nonproducer line Raji. Virology 133(1):146–157

    Article  CAS  PubMed  Google Scholar 

  • Poole BD, Schneider RI, Guthridge JM, Velte CA, Reichlin M, Harley JB, James JA (2009) Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus. Arthritis Rheum 60(3):848–859. doi:10.1002/art.24306

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rabson M, Heston L, Miller G (1983) Identification of a rare Epstein-Barr virus variant that enhances early antigen expression in Raji cells. Proc Natl Acad Sci USA 80(9):2762–2766

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Reedman BM, Klein G, Pope JH, Walters MK, Hilgers J, Singh S, Johansson B (1974) Epstein-Barr virus-associated complement-fixing and nuclear antigens in Burkitt lymphoma biopsies. Int J Cancer 13(6):755–763

    Article  CAS  PubMed  Google Scholar 

  • Reedman BM, Hilgers J, Hilgers F, Klein G (1975) Immunofluorescence and anti-complement immunofluorescence absorption tests for quantitation of Epstein-Barr virus-associated antigens. Int J Cancer 15(4):566–571

    Article  CAS  PubMed  Google Scholar 

  • Reischl U, Gerdes C, Motz M, Wolf H (1996) Expression and purification of an Epstein-Barr virus encoded 23-kDa protein and characterization of its immunological properties. J Virol Methods 57(1):71–85

    Article  CAS  PubMed  Google Scholar 

  • Rhodes G, Smith RS, Rubin RE, Vaughan J, Horwitz CA (1990) Identical IgM antibodies recognizing a glycine-alanine epitope are induced during acute infection with Epstein-Barr virus and cytomegalovirus. J Clin Lab Anal 4(6):456–464

    Article  CAS  PubMed  Google Scholar 

  • Robinson JE (1982) The biology of circulating B lymphocytes infected with Epstein-Barr virus during infectious mononucleosis. Yale J Biol Med 55(3–4):311–316

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ruprecht K, Wunderlich B, Gieß R, Meyer P, Loebel M, Lenz K, Hofmann J, Rosche B, Wengert O, Paul F, Reimer U, Scheibenbogen C (2014) Multiple sclerosis: the elevated antibody response to Epstein-Barr virus primarily targets, but is not confined to, the glycine-alanine repeat of Epstein-Barr nuclear antigen-1. J Neuroimmunol 272(1–2):56–61. doi:10.1016/j.jneuroim.2014.04.005

    Article  CAS  PubMed  Google Scholar 

  • Saridakis V, Sheng Y, Sarkari F, Holowaty MN, Shire K, Nguyen T, Zhang RG, Liao J, Lee W, Edwards AM, Arrowsmith CH, Frappier L (2005) Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Mol Cell 18(1):25–36

    Article  CAS  PubMed  Google Scholar 

  • Sears J, Ujihara M, Wong S, Ott C, Middeldorp J, Aiyar A (2004) The amino terminus of Epstein-Barr Virus (EBV) nuclear antigen 1 contains AT hooks that facilitate the replication and partitioning of latent EBV genomes by tethering them to cellular chromosomes. J Virol 78(21):11487–11505

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stevens SJ, Blank BS, Smits PH, Meenhorst PL, Middeldorp JM (2002) High Epstein-Barr virus (EBV) DNA loads in HIV-infected patients: correlation with antiretroviral therapy and quantitative EBV serology. AIDS 16(7):993–1001

    Article  CAS  PubMed  Google Scholar 

  • Stevens SJ, Smits PH, Verkuijlen SA, Rockx DA, van Gorp EC, Mulder JW, Middeldorp JM (2007) Aberrant Epstein-Barr virus persistence in HIV carriers is characterized by anti-Epstein-Barr virus IgA and high cellular viral loads with restricted transcription. AIDS 21(16):2141–2149

    Article  CAS  PubMed  Google Scholar 

  • Stolzenberg MC, Debouze S, Ng M, Sham J, Choy D, Bouguermouh A, Chan KH, Ooka T (1996) Purified recombinant EBV desoxyribonuclease in serological diagnosis of nasopharyngeal carcinoma. Int J Cancer 66(3):337–341

    Article  CAS  PubMed  Google Scholar 

  • Sugimoto A, Sato Y, Kanda T, Murata T, Narita Y, Kawashima D, Kimura H, Tsurumi T (2013) Different distributions of Epstein-Barr virus early and late gene transcripts within viral replication compartments. J Virol 87(12):6693–6699. doi:10.1128/JVI.00219-13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Summers WP, Grogan EA, Shedd D, Robert M, Liu CR, Miller G (1982) Stable expression in mouse cells of nuclear neoantigen after transfer of a 3.4-megadalton cloned fragment of Epstein-Barr virus DNA. Proc Natl Acad Sci USA 79(18):5688–5692

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Taylor GS, Long HM, Haigh TA, Larsen M, Brooks J, Rickinson AB (2006) A role for intercellular antigen transfer in the recognition of EBV-transformed B cell lines by EBV nuclear antigen-specific CD4 + T cells. J Immunol 177(6):3746–3756

    Article  CAS  PubMed  Google Scholar 

  • Thorley-Lawson DA, Geilinger K (1980) Monoclonal antibodies against the major glycoprotein (gp350/220) of Epstein-Barr virus neutralize infectivity. Proc Natl Acad Sci USA 77(9):5307–5311

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tolar P (2014) Spillane KM (2014) Force generation in B-cell synapses: mechanisms coupling B-cell receptor binding to antigen internalization and affinity discrimination. Adv Immunol 123:69–100. doi:10.1016/B978-0-12-800266-7.00002-9

    Article  CAS  PubMed  Google Scholar 

  • Tolar P, Sohn HW, Liu W, Pierce SK (2009) The molecular assembly and organization of signaling active B-cell receptor oligomers. Immunol Rev 232(1):34–41. doi:10.1111/j.1600-065X.2009.00833

    Article  CAS  PubMed  Google Scholar 

  • van Grunsven WM, Nabbe A, Middeldorp JM (1993a) Identification and molecular characterization of two diagnostically relevant marker proteins of the Epstein-Barr virus capsid antigen complex. J Med Virol 40(2):161–169

    Article  PubMed  Google Scholar 

  • van Grunsven WM, van Heerde EC, de Haard HJ, Spaan WJ, Middeldorp JM (1993b) Gene mapping and expression of two immunodominant Epstein-Barr virus capsid proteins. J Virol 67(7):3908–3916

    PubMed Central  PubMed  Google Scholar 

  • van Grunsven WM, Spaan WJ, Middeldorp JM (1994) Localization and diagnostic application of immunodominant domains of the BFRF3-encoded Epstein-Barr virus capsid protein. J Infect Dis 170(1):13–19

    Article  PubMed  Google Scholar 

  • Verschuuren E, van der Bij W, de Boer W, Timens W, Middeldorp J, The TH (2003) Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease. J Med Virol 69(2):258–266

    Article  PubMed  Google Scholar 

  • Verweij FJ, van Eijndhoven MA, Hopmans ES, Vendrig T, Wurdinger T, Cahir-McFarland E, Kieff E, Geerts D, van der Kant R, Neefjes J, Middeldorp JM, Pegtel DM (2011) LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation. EMBO J 30(11):2115–2129. doi:10.1038/emboj.2011.123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vroman B, Luka J, Rodriguez M, Pearson GR (1985) Characterization of a major protein with a molecular weight of 160,000 associated with the viral capsid of Epstein-Barr virus. J Virol 53(1):107–113

    PubMed Central  CAS  PubMed  Google Scholar 

  • Watt T, Oberfoell S, Balise R, Lunn MR, Kar AK, Merrihew L, Bhangoo MS, Montoya JG (2012) Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers. J Med Virol 84(12):1967–1974. doi:10.1002/jmv.23411

  • Winkelspecht B, Grässer F, Pees HW, Mueller-Lantzsch N (1996) Anti-EBNA1/anti-EBNA2 ratio decreases significantly in patients with progression of HIV infection. Arch Virol 141(5):857–864

    Article  CAS  PubMed  Google Scholar 

  • Wong KM, Levine AJ (1989) Characterization of proteins encoded by the Epstein-Barr virus transactivator gene BMLF1. Virology 168(1):101–111

    Google Scholar 

  • Woulfe JM, Gray MT, Gray DA, Munoz DG, Middeldorp JM (2014) Hypothesis: a role for EBV-induced molecular mimicry in Parkinson’s disease. Parkinsonism Relat Disord 20(7):685–694. doi:10.1016/j.parkreldis.2014.02.031

    Article  PubMed  Google Scholar 

  • Xu J, Ahmad A, Blagdon M, D’Addario M, Jones JF, Dolcetti R, Vaccher E, Prasad U, Menezes J (1998) The Epstein-Barr virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases. Int J Cancer 79(5):481–486

    Article  CAS  PubMed  Google Scholar 

  • Yadav P, Tran H, Ebegbe R, Gottlieb P, Wei H, Lewis RH, Mumbey-Wafula A, Kaplan A, Kholdarova E, Spatz L (2011) Antibodies elicited in response to EBNA-1 may cross-react with dsDNA. PLoS One 6(1):e14488. doi: 10.1371/journal.pone.001448810.1371/journal.pone.0014488

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yao QY, Rowe M, Morgan AJ, Sam CK, Prasad U, Dang H, Zeng Y, Rickinson AB (1991) Salivary and serum IgA antibodies to the Epstein-Barr virus glycoprotein gp340: incidence and potential for virus neutralization. Int J Cancer 48(1):45–50

    Article  CAS  PubMed  Google Scholar 

  • Zeng Y, Middeldorp JM, Madjar JJ, Ooka T (1997) A major DNA binding protein encoded by BALF2 open reading frame of Epstein-Barr virus (EBV) forms a complex with other EBV DNA-binding proteins: DNAase, EA-D, and DNA polymerase. Virology 239(2):285–295

    Article  CAS  PubMed  Google Scholar 

  • Zhang CX, Decaussin G, Daillie J, Ooka T (1988) Altered expression of two Epstein-Barr virus early genes localized in BamHI-A in nonproducer Raji cells. J Virol 62(6):1862–1869

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang PF, Klutch M, Armstrong G, Qualtiere L, Pearson G, Marcus-Sekura CJ (1991) Mapping of the epitopes of Epstein-Barr virus gp350 using monoclonal antibodies and recombinant proteins expressed in Escherichia coli defines three antigenic determinants. J Gen Virol 72(Pt 11):2747–2755

    Article  CAS  PubMed  Google Scholar 

  • Zur Hausen A, van Rees BP, van Beek J, Craanen ME, Bloemena E, Offerhaus GJ, Meijer CJ, van den Brule AJ (2004) Epstein-Barr virus in gastric carcinomas and gastric stump carcinomas: a late event in gastric carcinogenesis. J Clin Pathol 57(5):487–491

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Middeldorp, J.M. (2015). Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease . In: Münz, C. (eds) Epstein Barr Virus Volume 2. Current Topics in Microbiology and Immunology, vol 391. Springer, Cham. https://doi.org/10.1007/978-3-319-22834-1_10

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