Mechanism of human antibody-mediated neutralization of Marburg virus.
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.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Andrew I
AI
Flyak
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
Philipp A
PA
Ilinykh
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.
Charles D
CD
Murin
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
Tania
T
Garron
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
Xiaoli
X
Shen
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Marnie L
ML
Fusco
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Takao
T
Hashiguchi
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Zachary A
ZA
Bornholdt
Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Biostatistics, Vanderbilt University, Nashville, TN 37232, USA.
James C
JC
Slaughter
Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
Gopal
G
Sapparapu
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
Curtis
C
Klages
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
Thomas G
TG
Ksiazek
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Andrew B
AB
Ward
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.
Erica Ollmann
EO
Saphire
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
Alexander
A
Bukreyev
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.
James E
JE
Crowe
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000648:ultrastructure*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism; D008379:Marburg Virus Disease / Q000276:immunology*; D029024:Marburgvirus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; C081324:GP-protein, Marburg virus; D007140:Immunoglobulin Fab Fragments; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus