VirusesHerpesviridae

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

DomainMust know
Identity
  • dsDNA virus, family Herpesviridae (Human herpesvirus-4, HHV-4) [1]
  • Enveloped; linear dsDNA genome (~172 kb)
  • Acute infection → infectious mononucleosis; latent infection → virus hides in B-cells [1]
  • Up to 95% of the population may have latent EBV infection [1]
Reservoir / transmission
  • Humans are the only reservoir
  • Transmission via saliva ("kissing disease"), close contact
  • Also via blood products, organ transplant (rare)
  • EBV is endemic in Southern China / HK — relevant to NPC [3]
Key virulence
  • gp350 binds CD21 (CR2) on B-cells → B-cell entry and immortalisation
  • Latent membrane protein 1 (LMP1) mimics CD40 → constitutive NF-κB activation → B-cell proliferation
  • EBNA proteins maintain episomal latency in B-cells
  • Viral IL-10 homologue (BCRF1) → immune evasion
  • Different latency programmes (I/II/III) drive different malignancies
Clinical syndromes
  • Infectious mononucleosis: adolescents/young adults; fever, pharyngitis, LAD, splenomegaly, fatigue [1]
  • Atypical lymphocytosis on PBS (reactive CD8 T-cells; DDx: CMV, HIV, hepatitis, toxoplasma, drug reaction) [4]
  • Ampicillin/amoxicillin rash — classic exam trap
  • Splenic rupture risk (avoid contact sports 4–6 wks)
  • Nasopharyngeal carcinoma (NPC): endemic Southern China; IgA anti-VCA/EA; plasma EBV DNA for staging [1][3]
  • Burkitt lymphoma: endemic (African jaw); t(8;14) c-MYC/IgH
  • NK/T-cell (nasal-type) lymphoma: CD56+, EBV-associated [6]
  • Post-transplant lymphoproliferative disorder (PTLD): monitor EBV DNA in transplant recipients [2]
  • Hodgkin lymphoma (mixed cellularity subtype, EBV+ Reed-Sternberg cells)
  • Oral hairy leukoplakia (HIV/immunocompromised)
  • X-linked lymphoproliferative disease (Duncan syndrome; SH2D1A mutation)
Diagnosis
  • Monospot test (heterophile antibody): rapid screening for infectious mononucleosis [7]
  • EBV-specific serology: VCA-IgM (acute), VCA-IgG (past/current), EBNA-IgG (past infection)
  • EBV VCA-IgA and EA-IgA: screening for NPC (low specificity alone) [3]
  • Plasma EBV DNA by PCR: most sensitive tumour marker for NPC; monitors treatment response [3][8]
  • EDTA blood EBV DNA viral load: monitors PTLD in transplant recipients [2]
  • EBER in-situ hybridisation: gold standard for EBV in tissue (lymphoma, NPC)
  • PBS: atypical lymphocytes (DDx list is a favourite exam question) [4]
Treatment
  • Infectious mononucleosis: supportive (rest, analgesia, avoid contact sports)
  • Avoid ampicillin/amoxicillin → diffuse maculopapular rash
  • Short course corticosteroids: only if airway obstruction or severe thrombocytopenia
  • Antivirals (acyclovir/ganciclovir) have limited role in uncomplicated EBV
  • PTLD: reduce immunosuppression ± rituximab (anti-CD20) ± chemotherapy
  • NPC: concurrent chemoradiotherapy (cisplatin-based); advanced → immunotherapy
Prevention
  • No licensed EBV vaccine currently available
  • Transplant recipients: monitor EBV viral load for pre-emptive PTLD management [2]
  • NPC screening in high-risk populations (Southern China): EBV serology ± plasma EBV DNA [3]
Classic traps
  • Atypical lymphocytes DDx: EBV, CMV, HIV, acute viral hepatitis, toxoplasma, drug reaction — do NOT confuse with ALL blasts [4]
  • Monospot can be negative in children < 4 y → use EBV-specific serology
  • Plasma EBV DNA (not urine) is the most sensitive NPC tumour marker [8]
  • CMV mononucleosis: heterophile-negative, less prominent pharyngitis [5]
  • EBV VCA-IgA alone has low specificity for NPC; combine with plasma EBV DNA
  • NK/T-cell lymphoma is EBV-associated (not HPV or CMV) [6]

Exam Intelligence

On this page

No Headings