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.

In humans, the concentration of MBL in plasma varies greatly, ranging from a few nanograms per milliliter to 10,000 ng/ml due to polymorphisms in the promoter and exon 1 of the MBL2 gene (15) . Genetic variation in the MBL2 gene results in up to 30% of the human population having low blood MBL levels (Ͻ500 ng/ ml), which has been linked with an increased risk and severity of several infectious diseases (reviewed in references 17 and 44). Our in vitro results with DENV are consistent with this observation and provide a mechanism for why this occurs. The concept that levels of complement proteins could impact DENV severity is not new, as it was raised in seminal studies showing lower levels of C4 and C3 in patients with DHF/DSS (23) . Complement genetics (including MBL variation) and the susceptibility of DENV infection have also been examined. While one study observed an in- Serum MBL levels were measured by a quantitative capture ELISA as described in Materials and Methods. c Serum MBL binding to insect cell-derived DENV-2 virions was determined using a capture ELISA as described in the legend to Fig. 5D . Data are the means Ϯ standard deviations (SD) for four independent experiments. d MBL dependent-serum neutralization of insect cell-derived DENV-2 was performed as described in the legend to Fig. 5E . Neutralization was calculated based on reduction of the number of plaques compared to the value for heat-inactivated serum. Data are the means Ϯ SD for three independent experiments.