@article{8a850f9a0f704116969a98915ac449b9,
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.}",
note = "Funding Information: This project received support from the Defense Threat Reduction Agency (HDTRA1-13-1-0034) (to J.E.C.) and the U.S. NIH (1U19AI109711 to J.E.C. and A.B.; U19AI109762 to E.O.S. and A.B.W.; R01AI089498 and U01AI082156 to E.O.S.). E.O.S. is an Investigator in the Pathogenesis of Infectious Disease of the Burroughs Wellcome Fund. The project was supported by the NCRR (UL1 RR024975-01) and is now at the National Center for Advancing Translational Sciences (UL1 TR000445-06). T.H. received support from MEXT and JSPS Postdoctoral Fellowships for Research Abroad and a Research Fellowship of The Uehara Memorial Foundation. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank Dr. Eugene Agapov (Washington University in St. Louis) for useful suggestions concerning the generation of VSV/GP-Uganda escape mutants. We thank the donor, Dr. Norman Fujit (Wheat Ridge, Colorado), and the Vanderbilt Clinical Trials Center for help in sample acquisition. We thank Frances Smith-House, Gloria Fritz, Vidisha Singh, and Leland Brown for excellent technical support and Dr. Scott A. Smith for thoughtful comments and discussions. Flow cytometry experiments were performed in the VMC Flow Cytometry Shared Resource and supported by NIH grants (P30 CA68485 and DK058404). The EM work was conducted at the National Resource for Automated Molecular Microscopy at The Scripps Research Institute, which is supported by the Biomedical Technology Research Center program (GM103310) of the National Institute of General Medical Sciences. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = feb,
day = "26",
doi = "10.1016/j.cell.2015.01.031",
language = "English",
volume = "160",
pages = "893--903",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}
