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-Structure paper
Title | DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers. |
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Journal, issue, pages | Science, Vol. 349, Issue 6243, Page 88-91, Year 2015 |
Publish date | Jul 3, 2015 |
Authors | Guntur Fibriansah / Kristie D Ibarra / Thiam-Seng Ng / Scott A Smith / Joanne L Tan / Xin-Ni Lim / Justin S G Ooi / Victor A Kostyuchenko / Jiaqi Wang / Aravinda M de Silva / Eva Harris / James E Crowe / Shee-Mei Lok / |
PubMed Abstract | There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. ...There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics. |
External links | Science / PubMed:26138979 / PubMed Central |
Methods | EM (single particle) |
Resolution | 6.5 - 23.0 Å |
Structure data | EMDB-2967, PDB-4uif: EMDB-2968, PDB-4uih: EMDB-2969: EMDB-2996: Cryo-EM structure of Dengue virus serotype 2 strain PVP94/07 complexed with human antibody 2D22 Fab at 37 degrees C EMDB-2997: EMDB-2998: EMDB-2999: |
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Keywords | VIRAL PROTEIN / DENGUE VIRUS / HUMAN ANTIBODY / CRYO-EM / NEUTRALIZATION / DENGUE SEROTYPE 2 / VIRUS |