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Cell. 2015 Feb 26;160(5):893-903. doi: 10.1016/j.cell.2015.01.031.

Mechanism of human antibody-mediated neutralization of Marburg virus.

Author information

1
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
2
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
3
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
5
Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Biostatistics, Vanderbilt University, Nashville, TN 37232, USA.
6
Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
7
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
8
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
9
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.

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.

PMID:
25723164
PMCID:
PMC4344968
DOI:
10.1016/j.cell.2015.01.031
[Indexed for MEDLINE]
Free PMC Article

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