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Cell. 2015 Feb 26;160(5):904-912. doi: 10.1016/j.cell.2015.01.041.

Structural basis for Marburg virus neutralization by a cross-reactive human antibody.

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, 812-8582, Japan.
2
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Current address: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada.
4
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
5
Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
6
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, 812-8582, Japan.
7
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA.
8
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
9
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. Electronic address: erica@scripps.edu.

Abstract

The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of their NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. These structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry.

PMID:
25723165
PMCID:
PMC4344967
DOI:
10.1016/j.cell.2015.01.041
[Indexed for MEDLINE]
Free PMC Article

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