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TitleA Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms.
Journal, issue, pagesCell Rep, Vol. 31, Issue 4, Page 107584, Year 2020
Publish dateApr 28, 2020
AuthorsShuijun Zhang / Thomas Loy / Thiam-Seng Ng / Xin-Ni Lim / Shyn-Yun Valerie Chew / Ter Yong Tan / Meihui Xu / Victor A Kostyuchenko / Farhana Tukijan / Jian Shi / Katja Fink / Shee-Mei Lok /
PubMed AbstractHuman antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs ...Human antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs crosslink E protein dimers at extracellular pH 8.0 condition and also when further incubated at acidic endosomal conditions (pH 8.0-6.5). We observe Fab binding to DENV (pH 8.0-5.0) prevents virus fusion, and the number of bound Fabs increase (from 120 to 180). For ZIKV, although there are already 180 copies of Fab at pH 8.0, virus structural changes at pH 5.0 are not inhibited. The immunoglobulin G (IgG):DENV structure at pH 8.0 shows both Fab arms bind to epitopes around the 2-fold vertex. On ZIKV, an additional Fab around the 5-fold vertex at pH 8.0 suggests one IgG arm would engage with an epitope, although the other may bind to other viruses, causing aggregation. For DENV2 at pH 5.0, a similar scenario would occur, suggesting DENV2:IgG complex would aggregate in the endosome. Hence, a single antibody employs different neutralization mechanisms against different flaviviruses.
External linksCell Rep / PubMed:32348755
MethodsEM (single particle)
Resolution3.8 - 7.8 Å
Structure data

30192

7bu8

EMDB-30192, PDB-7bu8:
Cryo-EM structure of zika virus complexed with Fab SIgN-3C at pH 6.5
Method: EM (single particle) / Resolution: 3.8 Å

30193

7bua

EMDB-30193, PDB-7bua:
Cryo-EM structure of zika virus complexed with Fab SIgN-3C at pH 8.0
Method: EM (single particle) / Resolution: 4.8 Å

30194

7bub

EMDB-30194, PDB-7bub:
Cryo-EM structure of Dengue virus serotype 2 complexed with Fab SIgN-3C at pH 6.5
Method: EM (single particle) / Resolution: 4.2 Å

30195

7bud

EMDB-30195, PDB-7bud:
Cryo-EM structure of Dengue virus serotype 2 complexed with Fab SIgN-3C at pH 8.0
Method: EM (single particle) / Resolution: 4.5 Å

30196

7bue

EMDB-30196, PDB-7bue:
Cryo-EM structure of Dengue virus serotype 2 complexed with Fab SIgN-3C at pH 5.0
Method: EM (single particle) / Resolution: 7.8 Å

30197

7buf

EMDB-30197, PDB-7buf:
Cryo-EM structure of Dengue virus serotype 2 complexed with SIgN-3C IgG
Method: EM (single particle) / Resolution: 6.1 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • zika virus zikv/h. sapiens/frenchpolynesia/10087pf/2013
  • homo sapiens (human)
  • ZIKV (virus)
  • dengue virus 2
KeywordsVIRUS / Zika virus / antibody / neutralization / Dengue virus

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