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.

The 10.7-kb RNA genome of DENV contains genes that encode three structural proteins (capsid [C] , precursor membrane or membrane [prM/M], and envelope [E] ) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The mature dengue virion is an~50-nm particle composed of a nucleocapsid in association with the RNA genome, which is surrounded by a lipid bilayer into which the prM/M and E proteins insert. The E protein has two potential N-linked glycosylation sites, at Asn-67 in domain II, which is unique for the DENV complex, and Asn-153 in domain I, which is conserved in most flaviviruses (4) . DENV utilizes the N-linked glycan at Asn-67 to interact with the cell surface attachment lectin DC-SIGN to facilitate binding and entry into host cells (5, 6) . DENV enters cells via clathrin-mediated endocytosis and fuses with acidic endosomes, after which the viral genome penetrates into the cytoplasm of target cells (7) . Following protein translation and RNA replication, immature virions assemble within the endoplasmic reticulum (7) and pass through the Golgi and trans-Golgi network (8) where virus maturation and cleavage of prM to M protein are promoted by furin-like proteases (9) .