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TitleAn Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus.
Journal, issue, pagesImmunity, Vol. 48, Issue 4, Page 799-811.e9, Year 2018
Publish dateApr 17, 2018
AuthorsJoost Snijder / Michael S Ortego / Connor Weidle / Andrew B Stuart / Matthew D Gray / M Juliana McElrath / Marie Pancera / David Veesler / Andrew T McGuire /
PubMed AbstractEpstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have ...Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface. Integrating structural, biochemical, and infectivity data, we propose that AMMO1 inhibits fusion of the viral and cellular membranes. This work identifies a crucial epitope that may aid in the design of next-generation subunit vaccines against this major public health burden.
External linksImmunity / PubMed:29669253 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.55 - 10.0 Å
Structure data

7344

6c5v

EMDB-7344, PDB-6c5v:
An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-7345:
An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus
Method: EM (single particle) / Resolution: 10.0 Å

PDB-6bla:
Structure of AMM01 Fab, an anti EBV gH/gL neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 1.55 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER

ChemComp-GOL:
GLYCEROL

ChemComp-CL:
Unknown entry

ChemComp-TRS:
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / pH buffer*YM

ChemComp-2PE:
NONAETHYLENE GLYCOL / precipitant*YM

ChemComp-HOH:
WATER

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

Source
  • human herpesvirus 4 (Epstein-Barr virus)
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / SSGCID / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / antibody / Fab / EBV / gH/gL / VIRAL PROTEIN / Epstein-Barr virus / neutralizing antibodies / glycoproteins

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