HERPES VIRUS – EPSTEIN-BARR VIRUS

HERPES VIRUS – EPSTEIN-BARR VIRUS

• Epstein‑Barr virus (EBV) = human herpesvirus‑4, a double‑stranded DNA virus of the Herpesviridae family
• Transmission → saliva (kissing, sharing utensils), also blood, organ transplant, sexual contact
• Primary target cells → B‑lymphocytes (CD21/CR2 receptor) and nasopharyngeal epithelial cells

Clinical conditions caused by EBV

• Infectious mononucleosis (glandular fever) – fever, sore throat, lymphadenopathy, splenomegaly
• Burkitt’s lymphoma (endemic, sporadic, HIV‑associated) – jaw mass, abdominal tumor, starry‑sky histology
• Hodgkin’s lymphoma (mixed cellularity, lymphocyte‑rich)
• Nasopharyngeal carcinoma – painless nasal obstruction, epistaxis, cervical nodes
• Post‑transplant lymphoproliferative disorder (PTLD) – uncontrolled B‑cell proliferation in immunosuppressed hosts
• Oral hairy leukoplakia (HIV patients) – white corrugated plaques on lateral tongue
• Rare: hemophagocytic syndrome, encephalitis, myocarditis, Guillain‑Barré

Pathogenesis – stepwise flow

1. Virus in saliva contacts oropharyngeal epithelium →
2. Viral glycoprotein gp350 binds CD21 on B‑cells →
3. Fusion and entry → viral capsid releases DNA into nucleus →
4. Immediate‑early genes expressed → lytic replication in epithelial cells → release of virions →
5. Infection of naïve B‑cells → latency program (EBNA, LMP proteins) → B‑cell immortalisation →
6. Latent EBV persists in memory B‑cells → periodic re‑activation → shedding in saliva →
7. Host immune response (CD8⁺ T‑cells) controls lytic phase but cannot eradicate latent reservoir → chronic carrier state

Memory trick for pathogenesis
“Saliva Binds Cells Let It Re‑activate Continuously”
S = Saliva, B = B‑cell binding, C = Capsid entry, L = Latency, I = Immortalisation, R = Reactivation, C = Carrier

Morphology & laboratory features

• Enveloped icosahedral capsid, 150–200 nm diameter, linear dsDNA (~170 kb)
• Infected cells show “owl‑eye” nuclear inclusions (rare)
• Heterophile antibodies (IgM) produced in acute infection

Laboratory diagnosis

1. Heterophile (Monospot) test – rapid agglutination, positive in 80‑90 % of adolescents
2. EBV‑specific serology:
   • VCA‑IgM (early acute) → appears 1 wk, disappears 4–6 wk
   • VCA‑IgG (acute & past) → appears 1 wk, persists for life
   • EBNA‑IgG (latent) → appears 2–3 mo, persists lifelong
   • EA‑IgG (early antigen) → indicates active replication or re‑activation
3. PCR for EBV DNA in blood, throat wash, or tissue biopsy – quantitative load for PTLD or CNS disease
4. In situ hybridisation (EBER) on tissue sections – gold standard for EBV‑associated tumors
5. Complete blood count: lymphocytosis with atypical “Downey” cells, mild transaminase rise

Complications / sequelae

• Splenic rupture (especially in mononucleosis) → avoid contact sports for 3–4 weeks
• Autoimmune phenomena: hemolytic anemia, thrombocytopenia, Guillain‑Barré
• Malignancies listed above (Burkitt, Hodgkin, NPC, PTLD)
• Chronic fatigue syndrome (post‑infectious)

Management

• No specific antiviral proven; supportive care for mononucleosis (hydration, analgesics, antipyretics)
• Corticosteroids only for severe airway obstruction or hemolysis
• Rituximab (anti‑CD20) for EBV‑driven PTLD or severe lymphoma
• Monitor splenic size; advise activity restriction
• Counsel on transmission → avoid sharing drinks, mouth‑to‑mouth contact during acute phase

Prevention

• No vaccine currently available
• Good oral hygiene, avoid sharing utensils, screen donors for EBV in transplant settings

Exam tip – Remember the “V‑C‑L‑I‑R‑C” sequence:
V = Virus entry, C = Capsid release, L = Latency, I = Immortalisation, R = Reactivation, C = Carrier state. This covers the core steps asked in MUHS/NCH pathology questions.