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Molecular Mechanisms Involved in Antibody‐Dependent Enhancement of Dengue Virus Infection in Humans
Author(s) -
Flipse Jacky,
Wilschut Jan,
Smit Jolanda M.
Publication year - 2013
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12012
Subject(s) - dengue virus , antibody dependent enhancement , dengue fever , biology , virology , virus , antibody , immunology , immunity , flavivirus , immune system
Dengue is the most common arthropod-borne viral infection in humans with ∼50 million cases annually worldwide. In recent decades, a steady increase in the number of severe dengue cases has been seen. Severe dengue disease is most often observed in individuals that have pre-existing immunity against heterotypic dengue subtypes and in infants with low levels of maternal dengue antibodies. The generally accepted hypothesis explaining the immunopathogenesis of severe dengue is called antibody-dependent enhancement of dengue infection. Here, circulating antibodies bind to the newly infecting virus but do not neutralize infection. Rather, these antibodies increase the infected cell mass and virus production. Additionally, antiviral responses are diminished allowing massive virus particle production early in infection. The large infected cell mass and the high viral load are prelude for severe disease development. In this review, we discuss what is known about the trafficking of dengue virus in its human host cells, and the signalling pathways activated after virus detection, both in the absence and presence of antibodies against the virus. This review summarizes work that aims to better understand the complex immunopathogenesis of severe dengue disease.