Sudan virus (genus Ebolavirus) is lethal, yet no monoclonal antibody is known to neutralize it. We here describe antibody 16F6 that neutralizes Sudan virus and present its structure bound to the trimeric viral glycoprotein. Unexpectedly, the 16F6 epitope overlaps that of KZ52, the only other antibody against the GP1,2 core to be visualized to date. Furthermore, both antibodies against this crucial epitope bridging GP1–GP2 neutralize at a post-internalization step—probably fusion.
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We thank D. Burton and A. Hessell (The Scripps Research Institute, TSRI) for KZ52, M. Whitt (University of Tennessee Health Science Center) and D. Lyles (Wake Forest University School of Medicine) for anti-VSV IgG 23H12, J. Cunningham (Brigham and Women's Hospital) for rabbit anti-GP1 polyclonal antibody and I. Wilson of TSRI for critical reading of the manuscript. We would also like to thank C. Corbaci (TSRI) for assistance in figure preparation and the staff of the Advanced Photon Source Beamline 19-ID and the Advanced Light Source Beamlines 8.2.2 and 8.3.1 for assistance and for the use of their US Department of Energy–supported facilities. E.O.S. wishes to acknowledge US National Institutes of Health (NIH) grant U01 AI070530, the Skaggs Institute for Chemical Biology, a Career Award in the Biomedical Sciences and an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Welcome Fund. K.C. acknowledges support from NIH grants R01 AI088027 and R21 AI082437 and from institutional funds of the Albert Einstein College of Medicine. A.C.W. was supported by NIH training grants T32 GM007288 and T32 AI070117. Y.K. acknowledges support from NIH R01 AI055519 and membership within and support from the Region V 'Great Lakes' Regional Center for Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) Program (NIH award 2 U54 AI057153). J.M. Dye wishes to acknowledge support from the Defense Threat Reduction Agency (DTRA K.K0001_07_RD_B). Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Army.
The authors declare no competing financial interests.
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Dias, J., Kuehne, A., Abelson, D. et al. A shared structural solution for neutralizing ebolaviruses. Nat Struct Mol Biol 18, 1424–1427 (2011). https://doi.org/10.1038/nsmb.2150
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