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TitleA distinct E dimer epitope underlies selective recognition by a protective human West Nile virus antibody.
Journal, issue, pagesEMBO Rep, Vol. 27, Issue 15, Page 4583-4601, Year 2026
Publish dateJun 29, 2026
AuthorsBaldeep Khare / Charles-Adrien Arnaud / Thomas Klose / James E Crowe / Richard J Kuhn /
PubMed AbstractHuman outbreaks of West Nile virus (WNV) are an imminent threat in North America, with many annual infections and numerous cases of severe neuroinvasive disease. There are no licensed treatments for ...Human outbreaks of West Nile virus (WNV) are an imminent threat in North America, with many annual infections and numerous cases of severe neuroinvasive disease. There are no licensed treatments for WNV disease. Previous research identified WNV-86 as an ultrapotent neutralizing human antibody that binds domain II of the major envelope (E) glycoprotein in mature virions. Here, we report the structure of mature WNV in complex with the Fab of WNV-86, at a resolution of 3.8 Å, solved using cryogenic electron microscopy. Structure-based epitope mapping identifies a new class of E dimer epitope (EDE) antibodies that we designate as EDE3 antibodies. A partial overlap of WNV-86 and pre-membrane protein (prM) binding regions at more than one site ensures selective binding of WNV-86 to mature virions. The structure reveals the quaternary epitope of the neutralizing Fab and supports a model in which engaging both protomers of the dimer likely interferes with fusion-triggering rearrangements. This study identifies critical residues for binding, neutralization, and immune escape and clarifies the promise of this molecule for future immunotherapeutic interventions.
External linksEMBO Rep / PubMed:42373829 / PubMed Central
MethodsEM (single particle)
Resolution3.8 Å
Structure data

48850

9n3b

EMDB-48850, PDB-9n3b:
CryoEM structure of WNV (Kunjin strain) with the Fab of WNV-86 antibody
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

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

Source
  • kunjin virus
  • homo sapiens (human)
KeywordsVIRUS/IMMUNE SYSTEM / Complex / VIRUS / VIRUS-IMMUNE SYSTEM complex

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