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.

MBL neutralizes other DENV serotypes through complement-dependent and -independent mechanisms. The DENV complex comprises four antigenically related serotypes with significant diversity at the amino acid level (between 25 and 40%) (33) . We therefore extended our studies with MBL to the other serotypes of DENV. Consistent with results with DENV-2, MBL neutralized insect cell-derived DENV-1, -3, and -4 via complement-dependent (Fig. 6A ) and complement-independent (Fig. 6B) mechanisms. Naïve human sera from donor 1, which contained a higher level of MBL neutralized insect cell-derived DENV-1 and -3 more efficiently than sera from donor 2 (P Ͻ 0.001 for DENV-1 and P Ͻ 0.01 for DENV-3) (Fig. 6C) . However, sera from donor 1 (despite having a high concentration of MBL [~8 g/ml]) and donor 2 failed to neutralize insect cell-derived DENV-4 (Fig. 6C) . Nonetheless, reconstitution of serum from donor 2 with purified human MBL (1.36 g/ml) neutralized up to 90% of infection by DENV-1, -3, and -4 (Fig. 6C) , confirming that the complement-mediated neutralization of insect cell-derived DENV by human serum depended on MBL.