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This content will become publicly available on February 26, 2016

Title: Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody

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. We find that 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.
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [5] ;  [5] ;  [5] ;  [6] ;  [4] ;  [2]
  1. Scripps Research Inst., La Jolla, CA (United States); Kyushu Univ. (Japan)
  2. Scripps Research Inst., La Jolla, CA (United States)
  3. Scripps Research Inst., La Jolla, CA (United States); Univ. of Toronto, ON (Canada)
  4. Vanderbilt Univ., Nashville, TN (United States)
  5. Kyushu Univ. (Japan)
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
OSTI Identifier:
1239608
Grant/Contract Number:
U19 AI109762; R01 AI089498; R21AI069347; HDTRA1-13-1-0034; U19 AI109711; 26713018; 24115005; MINOS GM105404
Type:
Published Article
Journal Name:
Cell
Additional Journal Information:
Journal Volume: 160; Journal Issue: 5; Journal ID: ISSN 0092-8674
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES