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EMBO Mol Med. 2014 Mar;6(3):358-71. doi: 10.1002/emmm.201303404. Epub 2014 Jan 13.

A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface.

Author information

1
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore City, Singapore.

Abstract

Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross-reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype-specific and bind to quaternary structure-dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 Å resolution by cryo-EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI-DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection.

PMID:
24421336
PMCID:
PMC3958310
DOI:
10.1002/emmm.201303404
[Indexed for MEDLINE]
Free PMC Article

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