Dengue Antibody-Dependent Enhancement: Knowns and Unknowns
- 21 November 2014
- journal article
- review article
- Published by American Society for Microbiology in Microbiology Spectrum
- Vol. 2 (6), 249-271
- https://doi.org/10.1128/microbiolspec.aid-0022-2014
Abstract
Dengue provides the most abundant example in human medicine and the greatest human illness burden caused by the phenomenon of intrinsic antibody-dependent infection enhancement (iADE). In this immunopathological phenomenon infection of monocytes or macrophages using infectious immune complexes suppresses innate antiviral systems, permitting logarithmic intracellular growth of dengue virus. The four dengue viruses evolved from a common ancestor yet retain similar ecology and pathogenicity, but although infection with one virus provides short-term cross-protection against infection with a different type, millions of secondary dengue infections occur worldwide each year. When individuals are infected in the virtual absence of cross-protective dengue antibodies, the dengue vascular permeability syndrome (DVPS) may ensue. This occurs in around 2 to 4% of second heterotypic dengue infections. A complete understanding of the biologic mechanism of iADE, dengue biology, and the mechanism of host responses to dengue infection should lead to a comprehensive and complete understanding of the pathogenesis of DVPS. A crucial emphasis must be placed on understanding ADE. Clinical and epidemiological observations of DVPS define the research questions and provide research parameters. This article will review knowledge related to dengue ADE and point to areas where there has been little research progress. These observations relate to the two stages of dengue illnesses: afferent phenomena are those that promote the success of the microorganism to infect and survive; efferent phenomena are those mounted by the host to inhibit infection and replication and to eliminate the infectious agent and infected tissues. Data will be discussed as “knowns” and “unknowns.”Keywords
This publication has 100 references indexed in Scilit:
- Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infectionProceedings of the National Academy of Sciences of the United States of America, 2011
- Partial maturation: an immune-evasion strategy of dengue virus?Trends in Microbiology, 2011
- Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexesThe Lancet Infectious Diseases, 2010
- The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing ActivityCell Host & Microbe, 2010
- Dengue virus neutralization by human immune sera: Role of envelope protein domain III-reactive antibodyVirology, 2009
- Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibodyThe EMBO Journal, 2009
- Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus diseaseNature Medicine, 2008
- Dengue in Vietnamese Infants—Results of Infection‐Enhancement Assays Correlate with Age‐Related Disease Epidemiology, and Cellular Immune Responses Correlate with Disease SeverityThe Journal of Infectious Diseases, 2008
- Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue feverVirology, 2008
- Of cascades and perfect storms: the immunopathogenesis of dengue haemorrhagic fever‐dengue shock syndrome (DHF/DSS)Immunology & Cell Biology, 2006