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.

Flavivirus virions are dynamic structures, and their "breathing" at higher temperatures impacts antibody neutralization of WNV and DENV by modulating epitope accessibility (28, 29) , a phenomenon that could be important for antiviral immunity in the context of the febrile response. Consistent with this, binding of purified MBL to DENV at 37°C and 40°C increased neutralization of insect cell-derived DENV-2 (room temperature versus 37°C, P ϭ 0.02; room temperature versus 40°C, P ϭ 0.0009; 37°C versus 40°C, P Ͻ 0.0001), but not mammalian cell-derived DENV-2 in the absence of additional complement components ( Fig. 3A and B); this temperature effect was specific to MBL, as it was abolished by the addition of soluble mannan and did not occur with an irrelevant protein, bovine serum albumin (BSA), or another collectin, C1q.