Epstein-Barr Virus
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Direct answer
Epstein-Barr virus is a gamma herpesvirus that infects B lymphocytes through the oropharynx and stays latent for life in memory B cells. Primary infection in adolescents and young adults causes infectious mononucleosis, which is screened for by heterophile antibodies in the Monospot or Paul-Bunnell test. The virus is also linked to Burkitt lymphoma, nasopharyngeal carcinoma and Hodgkin lymphoma.
What you must remember
- Classification: Human gammaherpesvirus 4, a double-stranded DNA virus that enters B cells through the CD21 receptor.
- Transmission: Saliva is the main route, which is why infectious mononucleosis is called the kissing disease.
- Mononucleosis triad: Fever, pharyngitis and posterior cervical lymphadenopathy, often with splenomegaly and atypical lymphocytes.
- Heterophile antibodies: IgM agglutinates animal red cells and is detected by the Monospot; it is often negative in the first week and in young children.
- Specific serology: VCA IgM marks acute infection, while EBNA antibody appears late and persists for life.
- Endemic Burkitt lymphoma: Presents with jaw involvement in African children, carries the t(8;14) MYC translocation, and is linked to holoendemic malaria.
- Nasopharyngeal carcinoma: The undifferentiated type is strongly EBV associated.
- Post-transplant lymphoproliferative disorder: EBV-driven B-cell proliferation in immunosuppressed recipients, managed by reducing immunosuppression and using rituximab.
Choosing between heterophile tests and EBV serology
Heterophile tests answer the bedside question of mononucleosis, while specific antibodies answer the question of timing. The right test depends on which question the case is asking.
| Test | What it detects | Use when |
|---|---|---|
| Monospot or Paul-Bunnell | Heterophile IgM | Quick screen for mononucleosis |
| VCA IgM | Antibody to viral capsid antigen | Confirms acute primary infection |
| VCA IgG with EBNA IgG | Antibodies to capsid and nuclear antigens | Past infection with stable immunity |
| VCA IgG with EBNA absent | Early antibody profile, EBNA not yet produced | Recent infection |
EBNA appears late and then persists for life, so its absence alongside VCA IgG points to recent infection. Use the Monospot for the bedside question and the VCA panel when timing matters.
Read the results against the clinical story, because a single antibody value rarely settles a diagnosis. A young adult with classic symptoms and a positive Monospot needs no further serology in most settings. A patient with a negative Monospot, persistent fever or atypical features should prompt a search for other causes, such as cytomegalovirus or toxoplasmosis.
Where the exam tries to catch you
Mononucleosis questions usually hinge on what the test can and cannot detect.
- Trap: Ordering a negative Monospot in a child under four and dismissing mononucleosis. Correct: The test is often falsely negative in young children, so an EBV-specific antibody panel is needed.
- Trap: Prescribing ampicillin or amoxicillin for the sore throat of mononucleosis. Correct: Aminopenicillins cause a diffuse maculopapular rash in a high proportion of patients with mononucleosis, which is not a true allergy but should be avoided.
- Trap: Using steroids as routine treatment for mononucleosis. Correct: Steroids are reserved for airway obstruction, severe thrombocytopenia or haemolysis, and antivirals have no routine role.
- Trap: Assuming all Burkitt lymphoma is caused by EBV. Correct: EBV is linked to endemic and immunodeficiency-associated forms, while most sporadic Burkitt lymphomas are EBV negative.
Frequently asked questions
Which test is the classic screen for infectious mononucleosis?
The Monospot test, a rapid agglutination assay for heterophile antibodies, is the classic screen for infectious mononucleosis. Its sensitivity is low in the first week of illness and in young children, so a negative result does not exclude Epstein-Barr virus infection.
Why is ampicillin avoided in suspected infectious mononucleosis?
Ampicillin and amoxicillin cause a diffuse rash in a large proportion of patients with infectious mononucleosis, and this rash can be mistaken for penicillin allergy. Aminopenicillins should therefore be avoided in any patient with a sore throat until mononucleosis has been excluded or confirmed.
Which EBV-associated lymphoma is endemic in equatorial Africa?
Endemic Burkitt lymphoma, classically presenting with jaw involvement in children, is the EBV-associated lymphoma of equatorial Africa. Its occurrence is linked to co-infection with holoendemic malaria, a strong exam association.
What histological feature characterises Burkitt lymphoma?
Burkitt lymphoma shows a monomorphic population of medium-sized B cells with a starry-sky pattern, created by tingible body macrophages among the tumour cells. The t(8;14) translocation involving the MYC gene is its molecular hallmark.
Why does EBV serology change over time?
VCA IgM appears early in acute infection and falls over weeks, while EBNA antibody appears late and persists for life. Heterophile antibodies can persist for weeks to months, so reading these markers together helps estimate when Epstein-Barr virus infection occurred.