Epstein-Barr virus

EBV Virology - The Kissing Virus

• Family: Herpesviridae (Human herpesvirus 4, HHV-4).
• Structure: Large, enveloped virus with an icosahedral capsid containing a linear double-stranded DNA (dsDNA) genome.
• Transmission: Primarily through saliva (hence, "The Kissing Disease").
• Cellular Tropism: Targets oropharyngeal epithelial cells and B-lymphocytes by binding to the CD21 receptor.

⭐ EBV immortalizes B-cells by establishing a lifelong latent infection in memory B-cells, a critical step for its oncogenic potential.

Pathogenesis - B‑Cell Hijacker

EBV infects oropharyngeal epithelial cells and B-lymphocytes. Viral glycoprotein gp350 binds to the B-cell's CD21 receptor for entry, establishing lifelong latency within the memory B-cell pool. Viral proteins (LMPs, EBNAs) mimic constitutive activation signals (like CD40), driving relentless proliferation and preventing apoptosis. This "immortalizes" the B-cell, increasing the risk of malignant transformation.

⭐ EBV cleverly uses the CD21 receptor to enter B-cells. This receptor's normal job is to bind the C3d complement component, linking innate and adaptive immunity.

Infectious Mononucleosis - The Mono Show

• Classic Triad: Fever, lymphadenopathy (posterior cervical), and exudative pharyngitis.
  • Also, profound fatigue and malaise.
• Key Finding: Splenomegaly, present in ~50% of cases.
  • ⚠️ High risk of splenic rupture with contact sports/trauma.
• Lab Diagnosis:
  • Monospot test: Detects heterophile antibodies. Can be negative early in the illness.
  • Peripheral smear: Shows atypical lymphocytes (Downey cells).

⭐ Ampicillin Rash: A maculopapular rash frequently develops following administration of ampicillin or amoxicillin, but it is not a true drug allergy.

📌 Mnemonic (MONO):

• Monospot test
• Occipital (posterior cervical) lymphadenopathy
• No contact sports
• Only supportive care

Oncogenesis - Malignant Transformation

• EBV infects B-lymphocytes via the CD21 receptor, promoting cell growth and immortalization.
• Key viral oncoproteins drive malignant transformation:
  • LMP-1 (Latent Membrane Protein 1): A functional mimic of the CD40 receptor. It constitutively activates NF-κB and JAK/STAT pathways, upregulating anti-apoptotic proteins like Bcl-2.
  • EBNA-2 (EBV Nuclear Antigen 2): Transactivates host genes, including cyclin D, promoting cell cycle progression.
• This leads to polyclonal B-cell proliferation, which can result in malignancy if T-cell immunosurveillance is impaired.

⭐ The classic t(8;14) translocation in Burkitt lymphoma places the c-myc oncogene next to a highly active immunoglobulin heavy-chain promoter, leading to its overexpression.

Diagnosis - Lab Detectives

• Monospot Test: Rapidly detects heterophile antibodies (IgM) that agglutinate non-human RBCs. Note: Can be negative in the first week of illness or in young children.
• Peripheral Smear: Hallmark is a lymphocytosis with >10% atypical lymphocytes (Downey cells).
• EBV-Specific Antibodies: Definitive test if Monospot is negative.
  • VCA IgM: Acute infection.
  • VCA IgG: Acute/past infection.
  • EBNA: Past infection only.

⭐ Atypical lymphocytes are not the infected B cells, but the reactive cytotoxic T-lymphocytes (CD8+) responding to the infection.

• Epstein-Barr virus (EBV), a herpesvirus, primarily targets B-cells via the CD21 receptor, establishing a latent infection.
• Causes infectious mononucleosis ("kissing disease"), diagnosed by heterophile antibodies (Monospot test) and atypical lymphocytes.
• Strongly linked to cancers like Burkitt lymphoma (especially endemic African type), nasopharyngeal carcinoma, and mixed-cellularity Hodgkin lymphoma.
• In immunocompromised patients, it's associated with primary CNS lymphoma and oral hairy leukoplakia.