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.

Prospective cohort studies in children with preillness and acute plasma samples will be required to assess how a relative MBL deficiency impacts the severity of a primary DENV infection. Somewhat surprisingly, MBL in serum from donor 1 variably neutralized four serotypes of insect-cell derived DENV. Differential binding and neutralization of diverse HCV genotypes by MBL have also been observed (36) . Among the DENV serotypes, DENV-4 is the most antigenically distinct (50) . As the recognition of targets by MBL relies on surface-exposed carbohydrates, the extent of N-linked glycosylation and the spatial arrangement of glycans could influence susceptibility to MBL recognition and neutralization. Alternatively, differential maturation among DENV serotypes could affect retention and display of the prM glycoprotein on the virion and impact MBL binding and neutralization. Studies with different DENV serotypes produced in cells that overexpress furin are planned to address how maturation impacts MBL-dependent neutralization.