Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins

  title={Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins},
  author={Shee-Mei Lok and V. K. Kostyuchenko and Grant E. Nybakken and Heather A. Holdaway and Anthony J. Battisti and Soila Sukupolvi-Petty and Dagmar Sedlak and Daved H. Fremont and Paul Chipman and John T. Roehrig and Michael Steven Diamond and Richard J. Kuhn and Michael G. Rossmann},
  journal={Nature Structural \&Molecular Biology},
The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 °C, suggesting that the virus is in dynamic motion making hidden… 
On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes.
Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.
Antibody Binding Modulates Conformational Exchange in Domain III of Dengue Virus E Protein
This work provided one of the very rare descriptions of the effect of antibody binding on antigen dynamics, which was observed in the isolated DIII, in regions important for the packing of E protein dimers on the virus surface.
Impact of Quaternary Organization on the Antigenic Structure of the Tick-Borne Encephalitis Virus Envelope Glycoprotein E
Several important factors that influence the antigenicity of the flavivirus E protein and have an impact on the interaction with neutralizing antibodies are identified.
Structural insights into the neutralization mechanism of a higher primate antibody against dengue virus
It is shown that human sera from patients recovering from DENV‐4 infection contain antibodies that bind to the 5H2 epitope region on domain I, which provides new information and tools for effective vaccine design to prevent dengue disease.
Structural Changes in Dengue Virus When Exposed to a Temperature of 37°C
Cryo-electron microscopy images of dengue virus incubated at 37°C confirmed that the E protein shell has expanded and there is a hole at the 3-fold vertices, suggesting that all of the interdimeric and some intradimeric E protein interactions are weakened.
Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354
The cross-linking of the six E monomers within one raft by four CR4354 Fab fragments suggests that the antibody neutralizes WNV by blocking the pH-induced rearrangement of the E protein required for virus fusion with the endosomal membrane.
An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus
It is shown for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction.
Potent Dengue Virus Neutralization by a Therapeutic Antibody with Low Monovalent Affinity Requires Bivalent Engagement
We recently described our most potently neutralizing monoclonal antibody, E106, which protected against lethal Dengue virus type 1 (DENV-1) infection in mice. To further understand its functional


Variable Surface Epitopes in the Crystal Structure of Dengue Virus Type 3 Envelope Glycoprotein
The crystal structure of a soluble fragment of the envelope glycoprotein E from dengue virus type 3 is determined and shows that neighboring glycans on the viral surface are spaced widely enough that they can interact with multiple carbohydrate recognition domains on oligomeric lectins such as DC-SIGN, ensuring maximum affinity for these putative receptors.
Monoclonal Antibodies That Bind to Domain III of Dengue Virus E Glycoprotein Are the Most Efficient Blockers of Virus Adsorption to Vero Cells
The results indicate that most MAbs that neutralize virus infectivity do so, at least in part, by the blocking of virus adsorption, and provide the first direct evidence that domain III encodes the primary flavivirus receptor-binding motif.
Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica.
A set of murine monoclonal antibodies specific for the envelope (E) glycoprotein of DEN 2 virus is prepared and used in a comprehensive biological and biochemical analysis to identify 16 epitopes, which elicited potent neutralizers of virus infectivity and blocked hemagglutination, but did not block virus-mediated cell-membrane fusion.
Localization of a neutralizing epitope on the envelope protein of dengue virus type 2.
Two neutralization-resistant variants of dengue virus type 2 were selected using the neutralizing monoclonal antibody G8D11, and the epitope was sensitive to treatment with SDS and was dependent on the formation of a disulfide bridge.
West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody
The structure suggests that the E16 antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.
Type- and Subcomplex-Specific Neutralizing Antibodies against Domain III of Dengue Virus Type 2 Envelope Protein Recognize Adjacent Epitopes
Overall, the experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex- specific, and cross-reactive antibodies with different neutralizing potentials.
Structural basis of West Nile virus neutralization by a therapeutic antibody
The results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases, and potentially by blocking envelope glycoprotein conformational changes.