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.

Antibody-independent complement-mediated neutralization of both insect cell-and mammalian cell-derived DENV exclusively required MBL. Neutralization of DENV by MBL was dependent on MASP-2, partially dependent on C3, C4, factor D, and factor B, yet independent of C1q and C5. The absence of C3 or C4 alone only partially reduced neutralization, whereas a combined C3 and C4 deficiency nearly abolished serum neutralization. This suggests that direct binding of MBL neutralizes DENV through both the canonical lectin pathway and the C4 and C2 bypass pathways; in the latter, MBL binding directly triggers C3 activation independent of C4 and C2 (11) (12) (13) , resulting in deposition of C4 and C3 on the virion surface. The alternative pathway of complement activation partially contributed to DENV neutralization, presumably via the amplification loop, which leads to greater deposition of C3 on the virion surface (Fig. 1E) .