Epstein-Barr virus
Epstein-Barr virus is a double-stranded DNA herpesvirus (HHV-4) of the Lymphocryptovirus genus that causes infectious mononucleosis and is associated with Burkitt lymphoma, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disorder.
Organism Card
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Exam Intelligence
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Molecular Pathology Seminar (EBV): EBV is a dsDNA herpesvirus; acute infection = infectious mononucleosis; latent infection = virus hides in B-cells; up to 95% of the population may carry latent EBV [1]. This is a direct slide point — expect a stem testing basic virology classification.
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GC 101 (Diagnosis of Infections): EDTA blood EBV DNA viral load monitoring is used in bone marrow transplant recipients specifically for detecting post-transplant lymphoproliferative disorder (PTLD) for pre-emptive treatment [2]. This is the GC-framed reason to order EBV PCR in transplant patients — contrasted with CMV pp65 antigenaemia for CMV in solid organ transplant.
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NPC and EBV (Surgery/Felix Lai notes): EBV is the primary etiological agent in NPC pathogenesis [3]. Key serological markers: IgA against VCA and EA. Plasma circulating EBV DNA by PCR is used for diagnosis, staging, prognosis, treatment response, and recurrence detection. Pre-treatment plasma EBV DNA levels correlate with outcomes [3].
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Generalised lymphadenopathy lecture: Atypical lymphocytosis DDx = EBV, CMV, HIV, acute viral hepatitis, Mycoplasma, Legionella, disseminated TB, Talaromyces marneffei, Toxoplasma gondii, drug reactions [4]. Acute lymphoblastic leukaemia blasts can mimic atypical lymphocytes — classic trap to mention in SAQ.
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AOS Pathology: A case of bilateral nasal tumour with CD56+ malignant lymphoid cells (NK-cell lymphoma) — the answer is Epstein-Barr virus (not CMV, HIV, or HPV) [6]. This tests the EBV–extranodal NK/T-cell lymphoma association.
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2021 Fourth Summative MCQ Q19: 4-year-old girl with low-grade fever, sore throat, generalised maculopapular rash, atypical lymphocytes → answer = Monospot test (D) [7]. This is the direct past-paper test of EBV diagnosis in paediatrics.
- EBV vs CMV mononucleosis: Both cause atypical lymphocytes. EBV → exudative pharyngitis, splenomegaly, heterophile +ve. CMV → heterophile −ve, less prominent pharyngitis, more hepatitis [5]. In post-transplant: CMV = GI/retinitis/pneumonitis with inclusion bodies; EBV = PTLD.
- Ampicillin rash: Virtually pathognomonic vignette clue for EBV infectious mononucleosis. Not a true allergy — do not label patient as penicillin allergic.
- Monospot false negatives: Children < 4 years may not produce heterophile antibodies → must use EBV VCA-IgM for definitive acute diagnosis.
- EBV-associated malignancies spectrum: Burkitt lymphoma (endemic + sporadic), NPC, Hodgkin lymphoma (mixed cellularity), NK/T-cell lymphoma, PTLD, gastric carcinoma, leiomyosarcoma (in immunocompromised children). Exams love asking which virus is associated with each.
- NPC screening trap: EBV VCA-IgA has low specificity alone for NPC. Plasma EBV DNA is the most sensitive tumour marker [8] — this was directly tested in 2025 MCQ Q66.
2021 Fourth Summative MCQ Q19 [7]:
A 4-year-old girl presented with a low-grade fever, sore throat and a generalised, blanchable, erythematous, maculopapular rash. Her blood count revealed presence of atypical lymphocytes. [Select the MOST USEFUL test in patient diagnosis.]
- Answer: D. Monospot test
- Rationale: Classic infectious mononucleosis presentation with atypical lymphocytes. Monospot (heterophile antibody test) is the most useful rapid diagnostic test. Note: in young children, monospot sensitivity is lower, but it remains the best answer from the option list.
2025 Fourth Summative MCQ Q66 [8]:
Which of the following is the MOST SENSITIVE tumour marker for nasopharyngeal carcinoma? A. IgA against EA of EBV / B. IgA against VCA of Epstein-Barr virus (EBV) / C. Plasma EBV DNA / D. Urine EBV DNA
- Answer: C. Plasma EBV DNA
- Rationale: Plasma circulating EBV DNA detected by PCR is the most sensitive marker — used for diagnosis, staging, treatment response monitoring, and recurrence detection. IgA anti-VCA/EA are used for screening but have lower sensitivity and specificity. Urine EBV DNA is not a standard clinical test.
AOS Pathology EMQ [6]:
A 55-year-old man presents with bilateral nasal obstruction and on-and-off epistaxis for six months... Biopsy shows malignant lymphoid cells that are CD56 positive, compatible with NK-cell lymphoma. Which viral infection is most strongly associated with this disease?
- Answer: B. Epstein-Barr virus
- Rationale: Extranodal NK/T-cell lymphoma (nasal type) is strongly associated with EBV. EBER in-situ hybridisation is characteristically positive. Not HPV (oropharyngeal SCC), not CMV, not HIV.
2022 Fourth Summative MCQ Q21 [9]:
A 60-year-old woman with HBV-related cirrhosis received living donor liver transplantation 3 months ago... low-grade fever, abdominal pain, and diarrhoea for 5 days... Endoscopic biopsy of the inflamed sigmoid showed the presence of inclusion bodies.
- Answer: C. Cytomegalovirus (not EBV)
- Rationale: This is a discriminator question. Post-transplant GI disease with inclusion bodies = CMV colitis. EBV in post-transplant setting presents as PTLD (lymphoproliferative masses), not colitis with inclusion bodies. Know the difference.
2023 Fourth Summative MCQ Section B (Haematopoietic Neoplasms) [10]: The EMQ list includes "Post-transplant lymphoproliferative disease" as an option. While no specific stem in the indexed text directly describes a PTLD scenario, the inclusion signals this is examinable — expect a transplant patient with rising EBV viral load and lymphadenopathy/mass lesion → answer = PTLD.
[1] Lecture slides: Molecular Pathology Seminar 4_EPSTEIN-BARR VIRUS.pdf [2] Lecture slides: GC 101. Diagnosis of infections [Handouts].pdf [3] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (NPC section) [4] Senior notes: Block A - Generalised Lymphadenopathy_ Differential diagnosis and principle of management.pdf [5] Senior notes: Adrian Lui Pediatrics Notes.pdf (CMV section) [6] AOS material: AOS - Pathology.pdf [7] Past papers: 2021 Fourth Summative Assessment MCQ.pdf (Section B, Q19) [8] Past papers: 2025 Fourth Summative MCQ.pdf (Q66) [9] Past papers: 2022 Fourth Summative MCQ.pdf (Q21) [10] Past papers: 2023 Fourth Summative MCQ.pdf (Section B, Haematopoietic Neoplasms EMQ)