Mechanism of Human Antibody-Mediated Neutralization of Marburg Virus

نویسندگان

  • Andrew I. Flyak
  • Philipp A. Ilinykh
  • Charles D. Murin
  • Tania Garron
  • Xiaoli Shen
  • Marnie L. Fusco
  • Takao Hashiguchi
  • Zachary A. Bornholdt
  • James C. Slaughter
  • Gopal Sapparapu
  • Curtis Klages
  • Thomas G. Ksiazek
  • Andrew B. Ward
  • Erica Ollmann Saphire
  • Alexander Bukreyev
  • James E. Crowe
چکیده

The mechanisms by which neutralizing antibodies inhibit Marburg virus (MARV) are not known. We isolated a panel of neutralizing antibodies from a human MARV survivor that bind to MARV glycoprotein (GP) and compete for binding to a single major antigenic site. Remarkably, several of the antibodies also bind to Ebola virus (EBOV) GP. Single-particle EM structures of antibody-GP complexes reveal that all of the neutralizing antibodies bind to MARV GP at or near the predicted region of the receptor-binding site. The presence of the glycan cap or mucin-like domain blocks binding of neutralizing antibodies to EBOV GP, but not to MARV GP. The data suggest that MARV-neutralizing antibodies inhibit virus by binding to infectious virions at the exposed MARV receptor-binding site, revealing a mechanism of filovirus inhibition.

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عنوان ژورنال:
  • Cell

دوره 160  شماره 

صفحات  -

تاریخ انتشار 2015