Cellular and Molecular Basis of Antibody-Dependent Enhancement in Human Dengue Pathogenesis

Dengue fever is gaining increased attention as a major global health problem. It occurs annually in 50–100 million people in more than 100 countries, and places half a million people at risk of life-threatening diseases: dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). The pathogenic mechanisms causing DHF/DSS are not clearly understood. This article reviews cellular and molecular mechanisms that might be responsible for the initiation of the pathogenic processes, including hypotheses for DHF/DSS, dengue-permissive target cells, putative dengue receptors, neutralizing and enhancing antibodies to dengue virus, mechanisms of vascular plasma leakage, innate immune response in dengue infection and antibody-dependent enhancement of dengue infection. While reviewing the literature, the article also gives the author’s opinion on perceived areas of importance for future research in human dengue pathogenesis.