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 the absence of factor B (fB) or factor D (fD), DENV-2 neutralization was also partially inhibited, suggesting a contribution from the alternative pathway, probably via the amplification loop that results in greater deposition of C3 on the virion surface (Fig. 1E ). Serum from RAG1 Ϫ/Ϫ mice neutralized DENV infection to a level similar to that from wild-type mice; as RAG1 Ϫ/Ϫ mice lack B and T cells, this establishes that natural antibody does not contribute significantly to the serum-dependent neutralization of DENV-2. Notably, antibody-independent serum neutralization of DENV-2 was efficient, as even highly diluted (1.25% of neat) serum neutralized 60 to 70% of infection by DENV-2 ( Fig. 1B and D). MBL-dependent neutralization of both insect cell-and mammalian cell-derived DENV-2 by mouse serum was confirmed by a complete loss of neutralization in the presence of excess soluble mannan, a competitor for MBL binding ( Fig. 1B and D) .