Dengue virus causes two consecutive infections with different serotypes to produce dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Which immunological mechanism is responsible for the increased disease severity in secondary dengue infection?
- A Molecular mimicry — dengue proteins cross-react with platelet antigens
- B Original antigenic sin — memory B cells produce non-neutralizing antibodies of low avidity that enhance virus uptake by FcγR-bearing monocytes/macrophages (antibody-dependent enhancement, ADE) ✓
- C Superantigen effect of dengue NS1 protein activating polyclonal T cells
- D Complement depletion by dengue C3 convertase leading to secondary bacterial infections
Explanation
Antibody-dependent enhancement (ADE) is the dominant mechanism of severe dengue in secondary heterotypic infection. Memory B cells from the first infection produce cross-reactive but non-neutralizing IgG antibodies against the second serotype. These sub-neutralizing antibodies opsonize virus particles and facilitate their uptake via Fcγ receptors (FcγRII) on monocytes/macrophages, enormously increasing viral load (>100-fold) and triggering cytokine storm (TNF-α, IL-6, IL-8), plasma leakage, thrombocytopenia, and DHF/DSS. This is also the concern with dengue vaccines in seronegative individuals.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.