Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

Avirutnan, Panisadee; Hauhart, Richard E.; Marovich, Mary A.; Garred, Peter; Atkinson, John P.; Diamond, Michael S.

and member of the Flaviviridae family, which also includes West Nile virus (WNV), Japanese encephalitis virus, and yellow fever virus. DENV infection continues to spread globally with an estimated 70 to 100 human million infections, 2.1 million clinically severe cases, and 21,000 deaths per year (1) . Following mosquito inoculation, DENV infection in humans can be clinically silent (asymptomatic) or cause syndromes ranging from a febrile illness (classic dengue fever [DF] ) to a life-threatening hemorrhage and vascular permeability syndrome (dengue hemorrhagic fever/dengue shock syndrome [DHF/DSS]) (2) . Although the pathogenesis of DENV infection remains controversial, antibodydependent enhancement of DENV infection in Fc-␥ receptorbearing cells, effects of virulent strains, a proinflammatory cytokine storm secondary to exuberant activation of poorly lytic cross-reactive T cells, and excessive complement activation have been suggested as possible mechanisms (reviewed in reference 3).