Serological Testing for EBV - Principles and Uses of the Epstein-Barr Virus Antibody Test.

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EBV – Lifelong Infection

EBV can infect many cell types, but primarily infects the B lymphocytes. Over 90% of people are estimated to be infected with EBV by the time they reach adulthood. When infected in early childhood, symptoms are mild and undistinguishable from other common respiratory diseases.

If infection occurs later, in adolescence or young adulthood, it can cause infectious mononucleosis (IM) or ‘glandular fever’. This is a self-limiting condition that usually resolves within a couple of months. After the primary infection, which stimulates a strong immune response, the virus enters a latent phase. During this inactive phase, the viral genome is retained within a small number of B lymphocytes for the lifetime of the individual.

Serology – The Epstein-Barr Virus Antibody Test

Serology (the study of blood serum) is the diagnostic identification of antibodies in the serum. Serological tests for EBV can confirm primary infection and provide information on prior infection.

The Heterophile antibody test or ‘monospot test’ is a widely used lab technique first developed in 1932. The test is based on the observation that plasma/sera from patients with glandular fever can cause sheep red blood cells to clump. Modern versions of the test detect clumping of latex beads coated with bovine antigens. This Epstein-Barr virus antibody test is often used when patients have IM type symptoms (sore throat, fever, enlarged lymph glands, headache).

When the heterophile test is suspected to be a false-negative, a panel of specific tests can be carried out for antibodies against recombinant EBV proteins. Some of the viral proteins which we raise antibodies against include early antigen (EA), viral capsid antigen (VCA) and Epstein-Barr virus nuclear antigen (EBNA).

In general, primary infection is distinguished by a rise in anti-VCA antibodies, IM symptoms and a positive heterophile test. After symptoms resolve, the latent phase is characterized by detectable anti-EBNA and anti-VCA antibodies only. Anti-EA antibodies antibodies may reappear in cases of viral reactivation or EBV-related cancer.

EBV and Malignant Disease

EBV can drive infected cells to proliferate, resist natural cell death and hence become malignant. EBV appears to persist in tumor tissue, suggesting that the virus may contribute to maintaining the malignant phenotype.

Although rare in most countries, EBV-related cancers are estimated to affect around 1% of people worldwide. Populations most affected include southern China (nasopharyngeal carcinoma) and equatorial Africa (Burkitt’s Lymphoma).

EBV-related cancer is generally associated with high levels of serum antibodies against EA and VCA, but low levels against EBNA. However, results must be interpreted carefully, since similar laboratory findings can occur in non-malignant conditions such as autoimmune disease.

Viral DNA can be detected within tumor cells and hence can be used as a biomarker to monitor spread of disease or regression in response to therapy.


Laboratory Assays for Epstein-Barr Virus-Related Disease. M.Gulley and W.Tang. Journal of Molecular Diagnostics, July 2008, Vol 10 P279-292.

Epstein–Barr Virus-Associated Malignancies: Epidemiologic Patterns and Etiologic Implications J.Hsu & S.Glaser, Critical Reviews in Oncology/Hematology, 2000, Volume 34, Pages 27-53