Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever

Virus-Induced Decline in Soluble Vascular Endothelial Growth Receptor 2 Is Associated with Plasma Leakage in Dengue Hemorrhagic Fever

“…Prior exposure to dengue virus is a major risk factor for the development of plasma leakage in subsequent dengue virus infections (8). One of the proposed mechanisms is the presence of nonneutralizing antibodies, which facilitate viral uptake and replication (27). To determine whether dengue virus-specific antibodies can enhance infection of endothelial cells and the subsequent suppression of sVEGFR2 production, we inoculated HUVEC with virus at a low MOI of 2 in the presence of immune plasma, which was diluted beyond its neutralizing titer of 1:486.…”

Dengue and Dengue Hemorrhagic Fever

“…These data, along with epidemiologic observations that the majority of patients with reported DHF cases are experiencing a secondary infection, form the basis for the hypothesis that preexisting heterotypic dengue antibody is a risk factor for DHF (18,57,61,62,83,133). The lack of a good animal model for human disease and limitations of human clinical studies have made it difficult to confirm this hypothesis.…”

“…There is a large body of evidence, mostly obtained in vitro, suggesting that heterotypic, nonneutralizing antibody binds with dengue virus, facilitating the entry of the virus into cells of the monocytic line and hence facilitating infection (15,61,62,67,68,83). These data, along with epidemiologic observations that the majority of patients with reported DHF cases are experiencing a secondary infection, form the basis for the hypothesis that preexisting heterotypic dengue antibody is a risk factor for DHF (18,57,61,62,83,133).…”

Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001

“…The most accepted hypothesis to explain the development of serious illnesses by some people infected with dengue virus suggests that sequential infection with different serotypes followed by antibody-dependent enhancement of infection play a major role in the pathogenesis of DHF/DSS (2,14,15). However, DEN-1 circulating in America is capable of producing DHF/DSS even in people not affected by sequential infection.…”

“…Further studies incorporating additional DEN-2 strains resulted in the merging of genotypes II and III into one genotype (Asian/American-Asian genotype) (13). Infection by one serotype does not protect against infection by a second serotype, and epidemiologic and laboratory studies have shown that cross-reactive immune responses, including infection-enhancing antibodies, contribute to the higher frequency of DHF/DSS in persons with sequential infections (14,15). The occurrence of DHF/DSS in some regions has been associated with the introduction of new serotypes and/or genotypes of dengue virus (6,8,13,16).…”