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

doi:10.1016/j.cell.2015.01.031

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

Pathology

Research output: Contribution to journal › Article › peer-review

132 Scopus citations

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 language	English (US)
Pages (from-to)	893-903
Number of pages	11
Journal	Cell
Volume	160
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2015.01.031
State	Published - Feb 26 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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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

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title = "Mechanism of Human Antibody-Mediated Neutralization of Marburg Virus",

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.",

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

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year = "2015",

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day = "26",

doi = "10.1016/j.cell.2015.01.031",

language = "English (US)",

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AU - Flyak, Andrew I.

AU - Ilinykh, Philipp A.

AU - Murin, Charles D.

AU - Garron, Tania

AU - Shen, Xiaoli

AU - Fusco, Marnie L.

AU - Hashiguchi, Takao

AU - Bornholdt, Zachary A.

AU - Slaughter, James C.

AU - Sapparapu, Gopal

AU - Klages, Curtis

AU - Ksiazek, Thomas G.

AU - Ward, Andrew B.

AU - Saphire, Erica Ollmann

AU - Bukreyev, Alexander

AU - Crowe, James E.

PY - 2015/2/26

Y1 - 2015/2/26

N2 - 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.

AB - 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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Mechanism of Human Antibody-Mediated Neutralization of Marburg Virus

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