Mechanism of Human Antibody-Mediated Neutralization of Marburg Virus

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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)893-903
Number of pages11
JournalCell
Volume160
Issue number5
DOIs
StatePublished - Feb 26 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Flyak, A. I., Ilinykh, P. A., Murin, C. D., Garron, T., Shen, X., Fusco, M. L., Hashiguchi, T., Bornholdt, Z. A., Slaughter, J. C., Sapparapu, G., Klages, C., Ksiazek, T. G., Ward, A. B., Saphire, E. O., Bukreyev, A., & Crowe, J. E. (2015). Mechanism of Human Antibody-Mediated Neutralization of Marburg Virus. Cell, 160(5), 893-903. https://doi.org/10.1016/j.cell.2015.01.031