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Title | An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus. |
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Journal, issue, pages | Immunity, Vol. 48, Issue 4, Page 799-811.e9, Year 2018 |
Publish date | Apr 17, 2018 |
Authors | Joost Snijder / Michael S Ortego / Connor Weidle / Andrew B Stuart / Matthew D Gray / M Juliana McElrath / Marie Pancera / David Veesler / Andrew T McGuire / |
PubMed Abstract | 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 ...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 links | Immunity / PubMed:29669253 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.55 - 10.0 Å |
Structure data | EMDB-7344, PDB-6c5v: EMDB-7345: PDB-6bla: |
Chemicals | ChemComp-EDO: ChemComp-PEG: ChemComp-GOL: ChemComp-CL: ChemComp-TRS: ChemComp-2PE: ChemComp-HOH: ChemComp-NAG: |
Source |
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Keywords | IMMUNE SYSTEM / SSGCID / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / antibody / Fab / EBV / gH/gL / VIRAL PROTEIN / Epstein-Barr virus / neutralizing antibodies / glycoproteins |