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Structure paper

TitleStructural Basis of Protection against H7N9 Influenza Virus by Human Anti-N9 Neuraminidase Antibodies.
Journal, issue, pagesCell Host Microbe, Vol. 26, Issue 6, Page 729-738.e4, Year 2019
Publish dateDec 11, 2019
AuthorsXueyong Zhu / Hannah L Turner / Shanshan Lang / Ryan McBride / Sandhya Bangaru / Iuliia M Gilchuk / Wenli Yu / James C Paulson / James E Crowe / Andrew B Ward / Ian A Wilson /
PubMed AbstractInfluenza virus neuraminidase (NA) is a major target for small-molecule antiviral drugs. Antibodies targeting the NA surface antigen could also inhibit virus entry and egress to provide host ...Influenza virus neuraminidase (NA) is a major target for small-molecule antiviral drugs. Antibodies targeting the NA surface antigen could also inhibit virus entry and egress to provide host protection. However, our understanding of the nature and range of target epitopes is limited because of a lack of human antibody structures with influenza neuraminidase. Here, we describe crystal and cryogenic electron microscopy (cryo-EM) structures of NAs from human-infecting avian H7N9 viruses in complex with five human anti-N9 antibodies, systematically defining several antigenic sites and antibody epitope footprints. These antibodies either fully or partially block the NA active site or bind to epitopes distant from the active site while still showing neuraminidase inhibition. The inhibition of antibodies to NAs was further analyzed by glycan array and solution-based NA activity assays. Together, these structural studies provide insights into protection by anti-NA antibodies and templates for the development of NA-based influenza virus vaccines and therapeutics.
External linksCell Host Microbe / PubMed:31757767 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.12 - 3.6 Å
Structure data

EMDB-20538: CryoEM map of NA-22 Fab in complex with N9 Shangahi2
PDB-6pzw: CryoEM derived model of NA-22 Fab in complex with N9 Shanghai2
Method: EM (single particle) / Resolution: 3 Å

EMDB-20540: CryoEM map of NA-73 Fab in complex with N9 Shanghai2
PDB-6pzy: CryoEM derived model of NA-73 Fab in complex with N9 Shanghai2
Method: EM (single particle) / Resolution: 3.17 Å

EMDB-20541: CryoEM map of NA-80 Fab in complex with N9 Shangahi2
PDB-6pzz: CryoEM derived model of NA-80 Fab in complex with N9 Shanghai2
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-20594, PDB-6u02:
CryoEM-derived model of NA-63 Fab in complex with N9 Shanghai2
Method: EM (single particle) / Resolution: 3.05 Å

PDB-6pzd:
Crystal structure of the neuraminidase stabilization mutant Y169aH from A/Shanghai/2/2013 (H7N9)
Method: X-RAY DIFFRACTION / Resolution: 1.12 Å

PDB-6pze:
Crystal structure of human NA-45 Fab in complex with neuraminidase Y169aH mutant from A/Shanghai/2/2013 (H7N9)
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

PDB-6pzf:
Crystal structure of human NA-63 Fab in complex with neuraminidase from A/Hunan/02650/2016(H7N9)
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

PDB-6pzg:
Crystal structure of human NA-80 Fab
Method: X-RAY DIFFRACTION / Resolution: 1.59 Å

PDB-6pzh:
Crystal structure of human NA-22 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-MES:
2-(N-MORPHOLINO)-ETHANESULFONIC ACID / pH buffer*YM / MES (buffer)

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-CA:
CALCIUM ION / Calcium

ChemComp-HOH:
WATER / Water

ChemComp-PO4:
PHOSPHATE ION / Phosphate

Source
  • influenza a virus (a/environment/shanghai/s1439/2013(h7n9))
  • homo sapiens (human)
  • influenza a virus (a/shanghai/02/2013(h7n9))
  • influenza a virus (a/hunan/02650/2016(h7n9)
KeywordsAnimals / Antibodies, Monoclonal / Antibodies, Neutralizing / Antibodies, Viral / Antiviral Agents / Cryoelectron Microscopy / Epitopes / Humans / Influenza A Virus, H7N9 Subtype / Influenza Vaccines / Neuraminidase / Orthomyxoviridae Infections / Viral Proteins / VIRAL PROTEIN / antibody / inhibition mechanism / IMMUNE SYSTEM / VIRAL PROTEIN/IMMUNE SYSTEM / Sh2 / N9Shanghai / N9Sh2 / Fab / NA-22 / Influenza / VIRAL PROTEIN-IMMUNE SYSTEM complex / H7N9 / NA-73 / NA-80 / NA-63

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