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Chapter 72 : Epstein-Barr Virus

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Abstract:

Epstein-Barr virus (EBV) is generally acquired by oral transmission of virus in saliva. EBV has been linked with several human tumors including Hodgkin’s disease, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, some T-cell lymphomas, and leiomyosarcomas and B-cell lymphomas, especially in the central nervous system, in immunocompromised persons and organ transplant recipients. The Paul-Bunnell heterophile antibody associated with acute infectious mononucleosis agglutinates sheep and horse erythrocytes, among others, and is adsorbed by beef erythrocytes but not guinea pig kidney cells. The determination of IgM antibody to viral capsid antigen (VCA) (IgM-VCA) is the most valuable serologic procedure to diagnose acute EBV infection; antibody panels that do not include IgM-VCA are not as dependable for detection of acute EBV infection. High levels of IgA-VCA and IgA-EA are also found in persons with nasopharyngeal carcinoma, including the early asymptomatic stages. In these patients, tumor activity and response to cancer therapy may be monitored by serial IgA-VCA and IgA-EA determinations. Monoclonal antibodies directed against components of EBNA-1, EBNA-2, LMP-1, EA, VCA, and BZLF1 are commercially available, although the commercial EBNA-1 monoclonal antibody has not proved satisfactory for direct antigen detection. In situ hybridization is the most specific of these four molecular biological methods because it permits direct evaluation of individual cells. Similar to in situ hybridization, PCR is among the most sensitive methods available for detection of genomic EBV DNA. In addition to confirming EBV infection and showing the clonality, a ladder of smaller terminal digestion fragments, if present, from linear genomes indicates active EBV replication.

Citation: Jenson H. 2006. Epstein-Barr Virus, p 637-647. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch72

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Figures

Image of FIGURE 1
FIGURE 1

Schematic representation of the typical development of antibodies to various EBV antigens in patients with infectious mononucleosis, the prototype symptomatic primary EBV infection. The titers are geometric mean values expressed as reciprocals of the serum dilution. The minimum titers tested are 1:10 for VCA-IgG and EA, 1:8 for VCA-IgM, and 1:2.5 for EBNA. The IgM response to VCA is subdivided because of the significant differences noted according to age of the patient. (Adapted from references 8 and 18.)

Citation: Jenson H. 2006. Epstein-Barr Virus, p 637-647. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch72
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Image of FIGURE 2
FIGURE 2

EBV in situ hybridization with a digoxigenin-labeled EBER-1 riboprobe in a lymphoproliferative tumor in a patient with an immunodeficiency. EBV is detected in the majority of lymphocytes. A blood vessel is present in the upper left portion. The slide is counterstained with methyl green. Magnification, ×400. Photograph courtesy of Margaret L. Gulley.

Citation: Jenson H. 2006. Epstein-Barr Virus, p 637-647. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch72
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References

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1. Ambinder, R. F., and , R. B. Mann. 1994. Epstein-Barr-encoded RNA in situ hybridization. Diagnostic applications. Hum. Pathol. 25:602605.
2. Baumforth, K. R.,, L. S. Young,, K. J. Flavell,, C. Constandinou, and , P. G. Murray. 1999. The Epstein-Barr virus and its association with human cancers. Mol. Pathol. 6:307322.
3. Bruu, A. L.,, R. Hjetland,, F. Holter,, L. Mortensen,, O. Natås,, W. Petterson,, A. G. Skar,, T. Skarpaas,, T. Tjade, and , B. Åsjø. 2000. Evaluation of 12 commercial tests for detection of Epstein-Barr virus-specific and het-erophile antibodies. Clin. Diagn. Lab. Immunol. 7:451456.
4. Chang, R. S.,, J. P. Lewis, and , C. F. Abilgaard. 1973. Prevalence of oropharyngeal excretors of leukocyte-transforming agents among a human population. N. Engl. J. Med. 289:13251329.
5. Davidsohn, I., and , C. L. Lee. 1969. The clinical serology of infectious mononucleosis, p. 177200. In R. L. Carter and , H. G. Penman (ed.), Infectious Mononucleosis. Blackwell Scientific Publications, Oxford, United Kingdom.
6. de Schryver, A.,, G. Klein,, J. Hewetson,, G. Rocchi,, W. Henle,, G. Henle,, D. J. Moss, and , J. H. Pope. 1974. Comparison of EBV neutralization tests based on abortive infection or transformation of lymphoid cells and their relation to membrane reactive antibodies (anti-MA). Int. J. Cancer 13:353362.
7. Diaz-Mitoma, F.,, J. K. Preiksaitis,, W. C. Leung, and , D. L. J. Tyrrell. 1987. DNA-DNA dot hybridization to detect Epstein-Barr virus in throat washings. J. Infect. Dis. 155:297303.
8. Fleisher, G.,, W. Henle,, G. Henle,, E. T. Lennette, and , R. J. Biggar. 1979. Primary infection with Epstein-Barr virus in infants in the United States: clinical and serologic observations. J. Infect. Dis. 139:553558.
9. Glaser, S. L.,, M. L. Gulley,, M. J. Borowitz,, E. F. Craig,, R. B. Mann,, S. L. Stewart,, S. J. Shema, and , R. F. Ambinder. 2004. Inter- and intra-observer reliability of Epstein-Barr virus detection in Hodgkin lymphoma using histochemical procedures. Leuk. Lymphoma 45:489497.
10. Henle, G.,, W. Henle, and , G. Klein. 1971. Demonstration of two distinct components in the early antigen complex of Epstein-Barr virus-infected cells. Int. J. Cancer 8:272282.
11. Hubert, G. M. N.,, J. van Esser,, F. Fries,, K. C. Wolghers,, J. Cornelissen, and , A. D. M. F. Osterhaus. 2000. Development of a real-time quantitative assay for detection of Epstein-Barr virus. J. Clin. Microbiol. 38:712715.
12. ikuta, K.,, Y. Satoh,, Y. Hoshikawa, and , T. Sairenji. 2000. Detection of Epstein-Barr virus in salivas and throat washings in healthy adults and children. Microbes Infect. 2:115120.
13. Jenson, H. B. 2002. Infectious mononucleosis, p. 426436. In H. B. Jenson and , R. S. Baltimore (ed.), Pediatric Infectious Diseases: Principles and Practice. W. B. Saunders, Philadelphia, Pa.
14. Long, C.,, J. G. Derge, and , B. Hampar. 1974. Procedure for activating Epstein-Barr virus early antigen in nonpro-ducer cells by 5-iododeoxyuridine. J. Natl. Cancer Inst. 52:13551357.
15. Raab-Traub, N., and , K. Flynn. 1986. The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell 47:883889.
16. Reedman, B. M., and , G. Klein. 1973. Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int. J. Cancer 11:499520.
17. Rocchi, G.,, A. de Felici,, G. Ragona, and , A. Heinz. 1977. Quantitative evaluation of Epstein-Barr-virus-infected mononuclear peripheral blood leukocytes in infectious mononucleosis. N. Engl. J. Med. 296:132134.
18. Sumaya, C. V., and , Y. Ench. 1985. Epstein-Barr virus infectious mononucleosis in children. II. Heterophile antibody and viral-specific responses. Pediatrics 75:10111019.
19. Yamamoto, M.,, H. Kimura,, T. Hiromaka,, K. Hirai,, S. Hasegawa,, K. Kuzushima,, M. Shibata, and , T. Morishima. 1995. Detection and quantification of virus DNA in plasma of patients with Epstein-Barr virus-associated diseases. J. Clin. Microbiol. 33:17651768.

Tables

Generic image for table
TABLE 1

Tests used in the clinical diagnosis of EBV infection

Citation: Jenson H. 2006. Epstein-Barr Virus, p 637-647. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch72
Generic image for table
TABLE 2

Genomic origins of EBV targets commonly used for diagnosis of EBV infection

Citation: Jenson H. 2006. Epstein-Barr Virus, p 637-647. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch72
Generic image for table
TABLE 3

Correlation of clinical status and characteristic serologic responses to EBV infection

Citation: Jenson H. 2006. Epstein-Barr Virus, p 637-647. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch72
Generic image for table
TABLE 4

Summary of methodologies of EBV antigen systems classically used for detecting EBV-specific antibodies

Citation: Jenson H. 2006. Epstein-Barr Virus, p 637-647. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch72

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