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A Simple Flow Cytometry Based Assay to Determine In Vitro Antibody Dependent Enhancement of Dengue Virus Using Zika Virus Convalescent Serum
Published on: April 10, 2018
Antibodies determine virulence in dengue
1Supportive Research and Development Program, Pediatric Dengue Vaccine Initiative, Bethesda, Maryland 20852, USA. halsteads@erols.com
Annals of the New York Academy of Sciences
|September 16, 2009
Summary
Dengue hemorrhagic fever (DHF/DSS) is linked to heterotypic antibodies enhancing viral infection in monocytes. DENV 1 antibodies may protect against severe disease from American genotype DENV 2 infections.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Four dengue virus serotypes (DENV) cause a spectrum of illness, from mild to severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS).
- DHF/DSS is characterized by increased vascular permeability and is not caused by inherently virulent DENV strains.
- Severe dengue is associated with secondary infections in individuals with pre-existing heterotypic dengue antibodies at enhancing concentrations.
Purpose of the Study:
- To investigate the role of heterotypic antibodies in dengue pathogenesis.
- To understand the mechanisms by which antibodies influence DENV infection and disease severity.
- To explain the mild disease observed during secondary DENV infections with specific DENV genotypes.
Main Methods:
- Analysis of DENV infection in human monocytes/macrophages.
- Investigation of immune complex formation involving heterotypic antibodies and DENV envelope protein.
- Assessment of antibody-mediated effects on innate immunity and viral replication.
- Evaluation of clinical responses to primary and secondary DENV infections with different strains.
Main Results:
- Heterotypic antibodies, particularly those targeting domain I-II of the envelope protein, form immune complexes with DENV.
- These immune complexes bind to Fc receptors on monocytes/macrophages, suppressing innate immunity and increasing productive infection.
- Diverse clinical responses, including subclinical vascular permeability, occur during primary DENV infections.
- American (AM) genotype DENV 2 causes only mild disease during secondary infections, potentially due to DENV 1 antibodies downregulating disease via a unique antigenic structure on AM DENV 2.
Conclusions:
- Heterotypic antibodies play a critical role in the pathogenesis of severe dengue by enhancing viral infection in monocytes/macrophages.
- The interaction between antibodies, Fc receptors, and DENV is a key mechanism driving vascular permeability.
- Specific antibody responses, such as those from DENV 1 infection, can confer protection against severe disease caused by other DENV genotypes.
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