Open AccessA potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface
Author(s) -
Fibriansah Guntur,
Tan Joanne L,
Smith Scott A,
Alwis Adamberage R,
Ng ThiamSeng,
Kostyuchenko Victor A,
Ibarra Kristie D,
Wang Jiaqi,
Harris Eva,
Silva Aravinda,
Crowe James E,
Lok SheeMei
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303404
Subject(s) - library science , medical school , medicine , medical education , computer science
Dengue virus ( DENV ), which consists of four serotypes ( DENV 1‐4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies ( HMA bs) from dengue patients are cross‐reactive and poorly neutralizing. Rare neutralizing HMA bs are usually serotype‐specific and bind to quaternary structure‐dependent epitopes. We determined the structure of DENV 1 complexed with Fab fragments of a highly potent HMA b 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.