Chapter 99 : Epstein-Barr Virus

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This chapter focuses on Epstein-Barr virus (EBV) that is a member of the and belongs to the subfamily , replicating in epithelial cells and establishing long-term latency in lymphocytes like its closest human-pathogenic relative, human herpesvirus 8. EBV nuclear antigen 1 (EBNA1), EBNA2, EBNA3 (also referred to as EBNA3a), EBNA4 (EBNA3b), EBNA5 (EBNALP), EBNA6 (EBNA3c), and latent membrane proteins (LMP1, -2A, and -2B) may be expressed in B cells. Four types of B-cell latency have been defined, based on various levels of expression of the latency-associated proteins. During lytic replication more than 70 proteins are expressed, including the virus capsid antigens (VCA) and the early antigens used in diagnostics. Nucleic acid detection techniques (NAT) might be applied to blood, cerebrospinal fluid (CSF), or biopsy samples. A wide variety of detection methods are available, ranging from in situ hybridization on frozen or paraffin sections through cytohybridization on cell suspensions, dot blot hybridization, Southern blot hybridization, and nucleic acid amplification techniques (NAAT). The most commonly used clinical diagnostic tools for direct detection of EBV are NAAT. Quantitative real-time PCR is the most popular method today for EBV monitoring in patients at risk for EBV-associated disorders. Individual viral isolates can be characterized by molecular techniques on the basis of polymorphism of the EBNA1 and EBNA3 genes. Patients with X-linked lymphoproliferative syndrome have typically a high viral load and do not develop EBNA antibodies. The ultimate diagnosis, however, is based on genetic analysis for a variety of mutations in the SH2D1A gene domain.

Citation: Gärtner B. 2011. Epstein-Barr Virus , p 1575-1584. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch99

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Nucleic Acid Amplification Techniques
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Image of FIGURE 1

Development of antibodies to EBV antigens following primary infection. While there is marked interpatient and interlaboratory variation in titers, the typical relative development of titers by antibody class and antigen specificity is given.

Citation: Gärtner B. 2011. Epstein-Barr Virus , p 1575-1584. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch99
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Image of FIGURE 2

Diagnostic algorithm and interpretation scheme based on EBNA1 used with microparticle multiplex assays or rapid tests with random access in Europe. Diagnostic procedures and interpretation may start with EBNA1 IgG. If this parameter is positive, a past infection is proven; if EBNA1 IgG is negative, a negative VCA IgG results in the diagnosis of seronegative and a positive VCA IgM in the diagnosis of a primary infection. If VCA IgG is positive and the other parameters are negative, supplementary tests should be applied, e.g., avidity testing or blots using p18 antigen.

Citation: Gärtner B. 2011. Epstein-Barr Virus , p 1575-1584. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch99
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1. Bakker, N. A.,, E. A. Verschuuren,, M. E. Erasmus,, B. G. Hepkema,, N. J. Veeger,, C. G. Kallenberg,, and W. van der Bij. 2007. Epstein-Barr virus-DNA load monitoring late after lung transplantation: a surrogate marker of the degree of immunosuppression and a safe guide to reduce immunosuppression. Transplantation 83:433438.
2. Bauer, G. 2001. Simplicity through complexity: immunoblot with recombinant antigens as the new gold standard in Epstein-Barr virus serology. Clin. Lab. 47:223230.
3. Blaes, A. H.,, B. A. Peterson,, N. Bartlett,, D. L. Dunn,, and V. A. Morrison. 2005. Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial. Cancer 104:16611667.
4. Bonnet, F.,, A. C. Jouvencel,, M. Parrens,, M. J. Leon,, E. Cotto,, I. Garrigue,, P. Morlat,, J. Beylot,, H. Fleury,, and M. E. Lafon. 2006. A longitudinal and prospective study of Epstein-Barr virus load in AIDS-related non-Hodgkin lymphoma. J. Clin. Virol. 36:258263.
5. Bruu, A. L.,, R. Hjetland,, E. Holter,, L. Mortensen,, O. Natas,, W. Petterson,, A. G. Skar,, T. Skarpaas,, T. Tjade,, and B. Asjo. 2000. Evaluation of 12 commercial tests for detection of Epstein-Barr virus-specific and heterophile antibodies. Clin. Diagn. Lab. Immunol. 7:451456.
6. Chan, K. H.,, Y. L. Gu,, F. Ng,, P. S. Ng,, W. H. Seto,, J. S. Sham,, D. Chua,, W. Wei,, Y. L. Chen,, W. Luk,, Y. S. Zong,, and M. H. Ng. 2003. EBV specific antibody-based and DNA-based assays in serologic diagnosis of nasopharyngeal carcinoma. Int. J. Cancer 105:706709.
7. Chan, K. H.,, R. X. Luo,, H. L. Chen,, M. H. Ng,, W. H. Seto,, and J. S. Peiris. 1998. Development and evaluation of an Epstein-Barr virus (EBV) immunoglobulin M enzymelinked immunosorbent assay based on the 18-kilodalton matrix protein for diagnosis of primary EBV infection. J. Clin. Microbiol. 36:33593361.
8. Chen, M. R.,, M. Y. Liu,, S. M. Hsu,, C. C. Fong,, C. J. Chen,, I. H. Chen,, M. M. Hsu,, C. S. Yang,, and J. Y. Chen. 2001. Use of bacterially expressed EBNA-1 protein cloned from a nasopharyngeal carcinoma (NPC) biopsy as a screening test for NPC patients. J. Med. Virol. 64:5157.
9. Cherikh, W. S.,, H. M. Kauffman,, M. A. McBride,, J. Maghirang,, L. J. Swinnen,, and D. W. Hanto. 2003. Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation. Transplantation 76:12891293.
10. Choquet, S.,, V. Leblond,, R. Herbrecht,, G. Socie,, A. M. Stoppa,, P. Vandenberghe,, A. Fischer,, F. Morschhauser,, G. Salles,, W. Feremans,, E. Vilmer,, M. N. Peraldi,, P. Lang,, Y. Lebranchu,, E. Oksenhendler,, J. L. Garnier,, T. Lamy,, A. Jaccard,, A. Ferrant,, F. Offner,, O. Hermine,, A. Moreau,, S. Fafi-Kremer,, P. Morand,, L. Chatenoud,, N. Berriot-Varoqueaux,, L. Bergougnoux,, and N. Milpied. 2006. Efficacy and safety of rituximab in B-cell posttransplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood 107:30533057.
11. Cohen, J.I.,, H. Kimura,, S. Nakamura,, Y. H. Ko,, and E. S. Jaffe. 2009. Epstein-Barrvirus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report andsummary of an international meeting, 8-9 September 2008. Ann.Oncol. 20:14721482.
12. Connolly, Y.,, E. Littler,, N. Sun,, X. Chen,, P. C. Huang,, S. N. Stacey,, and J. R. Arrand. 2001. Antibodies to Epstein-Barr virus thymidine kinase: a characteristic marker for the serological detection of nasopharyngeal carcinoma. Int. J. Cancer 91:692697.
13. Crawford, D. H.,, A. J. Swerdlow,, C. Higgins,, K. McAulay,, N. Harrison,, H. Williams,, K. Britton,, and K. F. Macsween. 2002. Sexual history and Epstein-Barr virus infection. J. Infect. Dis. 186:731736.
14. Dardari, R.,, M. Khyatti,, A. Benider,, H. Jouhadi,, A. Kahlain,, C. Cochet,, A. Mansouri,, B. El Gueddari,, A. Benslimane,, and I. Joab. 2000. Antibodies to the Epstein-Barr virus transactivator protein (ZEBRA) as a valuable biomarker in young patients with nasopharyngeal carcinoma. Int. J. Cancer 86:7175.
15. Deyrup, A. T.,, V. K. Lee,, C. E. Hill,, W. Cheuk,, H. C. Toh,, S. Kesavan,, E. W. Chan,, and S. W. Weiss. 2006. Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients. Am. J. Surg. Pathol. 30:7582.
16. Elliott, S. L.,, A. Suhrbier,, J. J. Miles,, G. Lawrence,, S. J. Pye,, T. T. Le,, A. Rosenstengel,, T. Nguyen,, A. Allworth,, S. R. Burrows,, J. Cox,, D. Pye,, D. J. Moss,, and M. Bharadwaj. 2008. Phase I trial of a CD81 T-cell peptide epitope-based vaccine for infectious mononucleosis. J. Virol. 82:14481457.
17. Elstrom, R. L.,, C. Andreadis,, N. A. Aqui,, V. N. Ahya,, R. D. Bloom,, S. C. Brozena,, K. M. Olthoff,, S. J. Schuster,, S. D. Nasta,, E. A. Stadtmauer,, and D. E. Tsai. 2006. Treatment of PTLD with rituximab or chemotherapy. Am. J. Transplant. 6:569576.
18. Enbom, M.,, A. Strand,, K. I. Falk,, and A. Linde. 2001. Detection of Epstein-Barr virus, but not human herpesvirus 8, DNA in cervical secretions from Swedish women by real-time polymerase chain reaction. Sex. Transm. Dis. 28:300306.
19. Fafi-Kremer, S.,, P. Morand,, R. Germi,, M. Ballout,, J. P. Brion,, O. Genoulaz,, S. Nicod,, J. P. Stahl,, R. W. Ruigrok,, and J. M. Seigneurin. 2005. A prospective follow-up of Epstein-Barr virus LMP1 genotypes in saliva and blood during infectious mononucleosis. J. Infect. Dis. 192:21082111.
20. Fan, H.,, S. C. Kim,, C. O. Chima,, B. F. Israel,, K. M. Lawless,, P. A. Eagan,, S. Elmore,, D. T. Moore,, S. A. Schichman,, L. J. Swinnen,, and M. L. Gulley. 2005. Epstein-Barr viral load as a marker of lymphoma in AIDS patients. J. Med. Virol. 75:5969.
21. Fan, H.,, J. Nicholls,, D. Chua,, K. H. Chan,, J. Sham,, S. Lee,, and M. L. Gulley. 2004. Laboratory markers of tumor burden in nasopharyngeal carcinoma: a comparison of viral load and serologic tests for Epstein-Barr virus. Int. J. Cancer 112:10361041.
22. Gärtner, B.,, and J. K. Preiksaitis. 2010. EBV viral load detection in clinical virology. J. Clin. Virol. 48:8290.
23. Gärtner, B. C.,, J. M. Fischinger,, K. Roemer,, M. Mak,, B. Fleurent,, and N. Mueller-Lantzsch. 2001. Evaluation of a recombinant line blot for diagnosis of Epstein-Barr virus compared with ELISA, using immunofluorescence as reference method. J. Virol. Methods 93:8996.
24. Gärtner, B. C.,, R. D. Hess,, D. Bandt,, A. Kruse,, A. Rethwilm,, K. Roemer,, and N. Mueller-Lantzsch. 2003. Evaluation of four commercially available Epstein-Barr virus enzyme immunoassays with an immunofluorescence assay as the reference method. Clin. Diagn. Lab. Immunol. 10:7882.
25. Gärtner, B. C.,, K. Kortmann,, M. Schafer,, N. Mueller- Lantzsch,, U. Sester,, H. Kaul,, and H. Pees. 2000. No correlation in Epstein-Barr virus reactivation between serological parameters and viral load. J. Clin. Microbiol. 38:2458.
26. Gärtner, B. C.,, H. Schafer,, K. Marggraff,, G. Eisele,, M. Schafer,, D. Dilloo,, K. Roemer,, H. J. Laws,, M. Sester,, U. Sester,, H. Einsele,, and N. Mueller-Lantzsch. 2002. Evaluation of use of Epstein-Barr viral load in patients after allogeneic stem cell transplantation to diagnose and monitor posttransplant lymphoproliferative disease. J. Clin. Microbiol. 40:351358.
27. Gaspar, H. B.,, R. Sharifi,, K. C. Gilmour,, and A. J. Thrasher. 2002. X-linked lymphoproliferative disease: clinical, diagnostic and molecular perspective. Br. J. Haematol. 119:585595.
28. Grasser, F. A.,, P. G. Murray,, E. Kremmer,, K. Klein,, K. Remberger,, W. Feiden,, G. Reynolds,, G. Niedobitek,, L. S. Young,, and N. Mueller-Lantzsch. 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 84:37923798.
29. Gratama, J. W.,, M. A. Oosterveer,, W. Weimar,, K. Sintnicolaas,, W. Sizoo,, R. L. Bolhuis,, and I. Ernberg. 1994. Detection of multiple ‘Ebnotypes’ in individual Epstein-Barr virus carriers following lymphocyte transformation by virus derived from peripheral blood and oropharynx. J. Gen. Virol. 75 (Pt. 1):8594.
30. Gu, A. D.,, H. Y. Mo,, Y. B. Xie,, R. J. Peng,, J. X. Bei,, J. Peng,, M. Y. Li,, L. Z. Chen,, Q. S. Feng,, W. H. Jia,, and Y. X. Zeng. 2008. Evaluation of a multianalyte profiling assay and an enzyme-linked immunosorbent assay for serological examination of Epstein-Barr virus-specific antibody responses in diagnosis of nasopharyngeal carcinoma. Clin. Vaccine Immunol. 15:16841688.
31. Guerreiro-Cacais, A. O.,, L. Li,, D. Donati,, M. T. Bejarano,, A. Morgan,, M. G. Masucci,, L. Hutt-Fletcher,, and V. Levitsky. 2004. Capacity of Epstein-Barr virus to infect monocytes and inhibit their development into dendritic cells is affected by the cell type supporting virus replication. J. Gen. Virol. 85:27672778.
32. Gulley, M. L.,, and W. Tang. 2008. Laboratory assays for Epstein-Barr virus-related disease. J. Mol. Diagn. 10:279292.
33. Hakim, H.,, C. Gibson,, J. Pan,, K. Srivastava,, Z. Gu,, M. J. Bankowski,, and R. T. Hayden. 2007. Comparison of various blood compartments and reporting units for the detection and quantification of Epstein-Barr virus in peripheral blood. J. Clin. Microbiol. 45:21512155.
34. Haque, T.,, G. M. Wilkie,, M. M. Jones,, C. D. Higgins,, G. Urquhart,, P. Wingate,, D. Burns,, K. McAulay,, M. Turner,, C. Bellamy,, P. L. Amlot,, D. Kelly,, A. MacGilchrist,, M. K. Gandhi,, A. J. Swerdlow,, and D. H. Crawford. 2007. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood 110:11231131.
35. Henle, W.,, G. Henle,, J. Andersson,, I. Ernberg,, G. Klein,, C. A. Horwitz,, G. Marklund,, L. Rymo,, C. Wellinder,, and S. E. Straus. 1987. Antibody responses to Epstein-Barr virusdetermined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc. Natl. Acad. Sci. USA 84:570574.
36. Hess, R. D. 2004. Routine Epstein-Barr virus diagnostics from the laboratory perspective: still challenging after 35 years. J. Clin. Microbiol. 42:33813387.
37. Hoagland, R. J. 1964. The incubation period of infectious mononucleosis. Am. J. Public Health Nations Health 54:16991705.
38. Hurt, C.,, and D. Tammaro. 2007. Diagnostic evaluation ofmononucleosis-like illnesses. Am. J. Med. 120:911 e1911 e8.
39. Imashuku, S. 2002. Clinical features and treatment strategies of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Crit. Rev. Oncol. Hematol. 44:259272.
40. Iwatsuki, K.,, T. Yamamoto,, K. Tsuji,, D. Suzuki,, K. Fujii,, H. Matsuura,, and T. Oono. 2004. A spectrum of clinical manifestations caused by host immune responses against Epstein-Barr virus infections. Acta Med. Okayama 58:169180.
41. Jenson, H. B.,, C. T. Leach,, K. L. McClain,, V. V. Joshi,, B. H. Pollock,, R. T. Parmley,, E. G. Chadwick,, and S. B. Murphy. 1997. Benign and malignant smooth muscle tumors containing Epstein-Barr virus in children with AIDS. Leuk. Lymphoma 27:303314.
42. Junying, J.,, K. Herrmann,, G. Davies,, D. Lissauer,, A. Bell,, J. Timms,, G. M. Reynolds,, S. G. Hubscher,, L. S. Young,, G. Niedobitek,, and P. G. Murray. 2003. Absence of Epstein-Barr virus DNA in the tumor cells of European hepatocellular carcinoma. Virology 306:236243.
43. Kieff, E.,, and A. B. Rickinson,. 2007. Epstein-Barr virus andits replication, p. 26032654. In D. M. Knipe,, P. M. Howley,, D. E. Griffin,, R. A. Lamb,, M. A. Martin,, B. Roizman,, and S. E. Straus (ed.), Fields Virology, 5th ed., vol. 2. Lippincott Williams & Wilkins, Philadelphia, PA.
44. Kimura, H. 2006. Pathogenesis of chronic active Epstein- Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev. Med. Virol. 16:251261.
45. Kimura, H.,, T. Morishima,, H. Kanegane,, S. Ohga,, Y. Hoshino,, A. Maeda,, S. Imai,, M. Okano,, T. Morio,, S. Yokota,, S. Tsuchiya,, A. Yachie,, S. Imashuku,, K. Kawa,, and H. Wakiguchi. 2003. Prognostic factors for chronic active Epstein-Barr virus infection. J. Infect. Dis. 187:527533.
46. Knowles, D. M. 1997. Molecular pathology of acquired immunodeficiency syndrome-related non-Hodgkin’s lymphoma. Semin. Diagn. Pathol. 14:6782.
47. Landgren, O.,, E. S. Gilbert,, J. D. Rizzo,, G. Socie,, P. M. Banks,, K. A. Sobocinski,, M. M. Horowitz,, E. S. Jaffe,, D. W. Kingma,, L. B. Travis,, M. E. Flowers,, P. J. Martin,, H. J. Deeg,, and R. E. Curtis. 2009. Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation. Blood 113:49925001.
48. Lee, T. C.,, B. Savoldo,, C. M. Rooney,, H. E. Heslop,, A. P. Gee,, Y. Caldwell,, N. R. Barshes,, J. D. Scott,, L. J. Bristow,, C. A. O’Mahony,, and J. A. Goss. 2005. Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am. J. Transplant. 5:22222228.
49. Lennette, E. T.,, L. Rymo,, M. Yadav,, G. Masucci,, K. Merk,, L. Timar,, and G. Klein. 1993. Disease-related differences in antibody patterns against EBV-encoded nuclear antigens EBNA 1, EBNA 2 and EBNA 6. Eur. J. Cancer 29A:15841589.
50. Lennette, E. T.,, G. Winberg,, M. Yadav,, G. Enblad,, and G. Klein. 1995. Antibodies to LMP2A/2B in EBV-carrying malignancies. Eur. J. Cancer 31A:18751878.
51. Lin, J. C.,, W. Y. Wang,, W. M. Liang,, H. Y. Chou,, J. S. Jan,, R. S. Jiang,, J. Y. Wang,, C. W. Twu,, K. L. Liang,, J. Chao,, and W. C. Shen. 2007. Long-term prognostic effects of plasma Epstein-Barr virus DNA by minor groove binder-probe real-time quantitative PCR on nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 68:13421348.
52. Linde, A.,, B. Kallin,, J. Dillner,, J. Andersson,, L. Jagdahl,, A. Lindvall,, and B. Wahren. 1990. Evaluation of enzyme-linked immunosorbent assays with two synthetic peptides of Epstein- Barr virus for diagnosis of infectious mononucleosis. J. Infect. Dis. 161:903909.
53. Linderholm, M.,, J. Boman,, P. Juto,, and A. Linde. 1994. Comparative evaluation of nine kits for rapid diagnosis of infectious mononucleosis and Epstein-Barr virus-specific serology. J. Clin. Microbiol. 32:259261.
54. Ling, P. D.,, J. A. Lednicky,, W. A. Keitel,, D. G. Poston,, Z. S. White,, R. Peng,, Z. Liu,, S. K. Mehta,, D. L. Pierson,, C. M. Rooney,, R. A. Vilchez,, E. O. Smith,, and J. S. Butel. 2003. The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study. J. Infect. Dis. 187:15711580.
55. Maurmann, S.,, L. Fricke,, H. J. Wagner,, P. Schlenke,, H. Hennig,, J. Steinhoff,, and W. J. Jabs. 2003. Molecular parameters for precise diagnosis of asymptomatic Epstein-Barr virus reactivation in healthy carriers. J. Clin. Microbiol. 41:54195428.
56. Merlo, A.,, R. Turrini,, R. Dolcetti,, P. Zanovello,, A. Amadori,, and A. Rosato. 2008. Adoptive cell therapy against EBV-related malignancies: a survey of clinical results. Expert Opin. Biol. Ther. 8:12651294.
57. Middeldorp, J. M.,, A. A. Brink,, A. J. van den Brule,, and C. J. Meijer. 2003. Pathogenic roles for Epstein-Barr virus (EBV) gene products in EBV-associated proliferative disorders. Crit. Rev. Oncol. Hematol. 45:136.
58. Milone, M. C.,, D. E. Tsai,, R. L. Hodinka,, L. B. Silverman,, A. Malbran,, M. A. Wasik,, and K. E. Nichols. 2005. Treatment of primary Epstein-Barr virus infection in patients with X-linked lymphoproliferative disease using B-cell-directed therapy. Blood 105:994996.
59. Morra, M.,, D. Howie,, M. S. Grande,, J. Sayos,, N. Wang,, C. Wu,, P. Engel,, and C. Terhorst. 2001. X-linked lymphoproliferative disease: a progressive immunodeficiency. Annu. Rev. Immunol. 19:657682.
60. Niedobitek, G.,, and H. Herbst. 2006. In situ detection of Epstein-Barr virus and phenotype determination of EBVinfected cells. Methods Mol. Biol. 326:115137.
61. Papesch, M.,, and R. Watkins. 2001. Epstein-Barr virus infectious mononucleosis. Clin. Otolaryngol. Allied Sci. 26:38.
62. Petersen, I.,, J. M. Thomas,, W. T. Hamilton,, and P. D. White. 2006. Risk and predictors of fatigue after infectious mononucleosis in a large primary-care cohort. QJM 99:4955.
63. Plentz, A.,, W. Jilg,, B. Kochanowski,, B. Ibach,, and A. Knoll. 2008. Detection of herpesvirus DNA in cerebrospinal fluid and correlation with clinical symptoms. Infection 36:158162.
64. Preiksaitis, J. K.,, X. L. Pang,, J. D. Fox,, J. M. Fenton,, A. M. Caliendo,, and G. G. Miller. 2009. Interlaboratory comparison of Epstein-Barr virus viral load assays. Am. J. Transplant. 9:269279.
65. Randhawa, P. S.,, R. Jaffe,, A. J. Demetris,, M. Nalesnik,, T. E. Starzl,, Y. Y. Chen,, and L. M. Weiss. 1992. Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with posttransplantation lymphoproliferative disease. N. Engl. J. Med. 327:17101714.
66. Rickinson, A.B.,, and E. Kieff,. 2007. Epstein-Barrvirus, p. 26562700. In D. M. Knipe,, P. M. Howley,, D. E. Griffin,, R. A. Lamb,, M. A. Martin,, B. Roizman,, and S. E. Straus (ed.), Fields Virology, 5th ed., vol. 2. Lippincott Williams & Wilkins, Philadelphia, PA.
67. Savard, M.,, C. Belanger,, M. Tardif,, P. Gourde,, L. Flamand,, and J. Gosselin. 2000. Infection of primary human monocytes by Epstein-Barr virus. J. Virol. 74:26122619.
68. Sokal, E. M.,, K. Hoppenbrouwers,, C. Vandermeulen,, M. Moutschen,, P. Leonard,, A. Moreels,, M. Haumont,, A. Bollen,, F. Smets,, and M. Denis. 2007. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. J. Infect. Dis. 196:17491753.
69. Stevens, S. J.,, S. A. Verkuijlen,, B. Hariwiyanto,, Harijadi,, J. Fachiroh,, D. K. Paramita,, I. B. Tan,, S. M. Haryana,, and J. M. Middeldorp. 2005. Diagnostic value of measuring Epstein-Barr virus (EBV) DNA load and carcinoma-specific viral mRNA in relation to anti-EBV immunoglobulin A (IgA) and IgG antibody levels in blood of nasopharyngeal carcinoma patients from Indonesia. J. Clin. Microbiol. 43:30663073.
70. Studahl, M.,, L. Hagberg,, E. Rekabdar,, and T. Bergstrom. 2000. Herpesvirus DNA detection in cerebral spinal fluid: differences in clinical presentation between alpha-, beta-, and gamma-herpesviruses. Scand. J. Infect. Dis. 32:237248.
71. Sumaya, C. V.,, and Y. Ench. 1985. Epstein-Barr virus infectious mononucleosis in children. II. Heterophil antibody and viral-specific responses. Pediatrics 75:10111019.
72. Sumegi, J.,, T. A. Seemayer,, D. Huang,, J. R. Davis,, M. Morra,, T. G. Gross,, L. Yin,, G. Romco,, E. Klein,, C. Terhorst,, and A. Lanyi. 2002. A spectrum of mutations in SH2D1A that causes X-linked lymphoproliferative disease and other Epstein-Barr virus-associated illnesses. Leuk. Lymphoma 43:11891201.
73. Svahn, A.,, M. Magnusson,, L. Jagdahl,, L. Schloss,, G. Kahlmeter,, and A. Linde. 1997. Evaluation of three commercial enzyme-linked immunosorbent assays and two latex agglutination assays for diagnosis of primary Epstein-Barr virus infection. J. Clin. Microbiol. 35:27282732.
74. To, E. W.,, K. C. Chan,, S. F. Leung,, L. Y. Chan,, K. F. To,, A. T. Chan,, P. J. Johnson,, and Y. M. Lo. 2003. Rapid clearance of plasma Epstein-Barr virus DNA after surgical treatment of nasopharyngeal carcinoma. Clin. Cancer Res. 9:32543259.
75. Torre, D.,, and R. Tambini. 1999. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand. J. Infect. Dis. 31:543547.
76. Tranchand-Bunel, D.,, H. Gras-Masse,, B. Bourez,, L. Dedecker,, and C. Auriault. 1999. Evaluation of an Epstein-Barr virus (EBV) immunoglobulin M enzyme-linked immunosorbent assay using a synthetic convergent peptide library, or mixotope, for diagnosis of primary EBV infection. J. Clin. Microbiol. 37:23662368.
77. Trappe, R.,, H. Riess,, N. Babel,, M. Hummel,, H. Lehmkuhl,, S. Jonas,, I. Anagnostopoulos,, M. Papp-Vary,, P. Reinke,, R. Hetzer,, B. Dorken,, and S. Oertel. 2007. Salvage chemotherapy for refractory and relapsed posttransplant lymphoproliferative disorders (PTLD) after treatment with single-agent rituximab. Transplantation 83:912918.
78. Triantos, D.,, S. R. Porter,, C. Scully,, and C. G. Teo. 1997. Oral hairy leukoplakia: clinicopathologic features, pathogenesis, diagnosis, and clinical significance. Clin. Infect. Dis. 25:13921396.
79. Tynell, E.,, E. Aurelius,, A. Brandell,, I. Julander,, M. Wood,, Q. Y. Yao,, A. Rickinson,, B. Akerlund,, and J. Andersson. 1996. Acyclovir and prednisolone treatment of acute infectious mononucleosis: a multicenter, double-blind, placebocontrolled study. J. Infect. Dis. 174:324331.
80. van Grunsven, W. M.,, W. J. Spaan,, and J. M. Middeldorp. 1994. Localization and diagnostic application of immunodominant domains of the BFRF3-encoded Epstein-Barr virus capsid protein. J. Infect. Dis. 170:1319.
81. Vidrih, J. A.,, R. P. Walensky,, P. E. Sax,, and K. A. Freedberg. 2001. Positive Epstein-Barr virus heterophile antibody tests in patients with primary human immunodeficiency virus infection. Am. J. Med. 111:192194.
82. Wagner, H. J.,, G. Bein,, A. Bitsch,, and H. Kirchner. 1992. Detection and quantification of latently infected B lymphocytes in Epstein-Barr virus-seropositive, healthy individuals by polymerase chain reaction. J. Clin. Microbiol. 30:28262829.
83. Walensky, R. P.,, E. S. Rosenberg,, M. J. Ferraro,, E. Losina,, B. D. Walker,, and K. A. Freedberg. 2001. Investigation of primary human immunodeficiency virus infection in patients who test positive for heterophile antibody. Clin. Infect. Dis. 33:570572.
84. Walker, R. C.,, W. F. Marshall,, J. G. Strickler,, R. H. Wiesner,, J. A. Velosa,, T. M. Habermann,, C. G. McGregor,, and C. V. Paya. 1995. Pretransplantation assessment of the risk of lymphoproliferative disorder. Clin. Infect. Dis. 20:13461353.
85. Winkelspecht, B.,, F. Grasser,, H. W. Pees,, and N. Mueller- Lantzsch. 1996. Anti-EBNA1/anti-EBNA2 ratio decreases significantly in patients with progression of HIV infection. Arch. Virol. 141:857864.
86. Wong, J.,, S. Sibani,, N. N. Lokko,, J. LaBaer,, and K. S. Anderson. 2009. Rapid detection of antibodies in sera using multiplexed self-assembling bead arrays. J. Immunol. Methods 350:171182.
87. Xu, J.,, A. Ahmad,, M. D’Addario,, L. Knafo,, J. F. Jones,, U. Prasad,, R. Dolcetti,, E. Vaccher,, and J. Menezes. 2000. Analysis and significance of anti-latent membrane protein-1 antibodies in the sera of patients with EBV-associated diseases. J. Immunol. 164:28152822.
88. Yao, Q. Y.,, A. B. Rickinson,, and M. A. Epstein. 1985. A re-examination of the Epstein-Barr virus carrier state in healthy seropositive individuals. Int. J. Cancer 35:3542.


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Materials and methods used for diagnosis and monitoring of disease caused by EBV, for indication of EBV associated malignancies, or for verification of EBV association in diagnosed tumors

gEq, genome equivalents; XLP, X-linked lymphoproliferative syndrome.

Citation: Gärtner B. 2011. Epstein-Barr Virus , p 1575-1584. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch99
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Overview of commercial products for EBV diagnosis

ELISA, enzyme-linked immunosorbent assay; CLIA, chemiluminescent immunoassay; CMV, cytomegalovirus.

Citation: Gärtner B. 2011. Epstein-Barr Virus , p 1575-1584. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch99
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Typical EBV serologic profiles using ttblhe most frequently employed antigens and Ig isotypes

Atypical patterns include VCA IgM positive only, EBNA positive only, or VCA IgM and EBNA positive but VCA IgG negative. Atypical patterns merit repeat testing, testing of a follow-up sample, or testing by alternate methods. 6, antibodies absent or present in low titers; 1, antibodies present; 11, antibodies present in elevated titers; 111, antibodies present in strongly elevated titers.

Citation: Gärtner B. 2011. Epstein-Barr Virus , p 1575-1584. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch99

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