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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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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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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