Brief Communication | Published:

A shared structural solution for neutralizing ebolaviruses

Nature Structural & Molecular Biology volume 18, pages 14241427 (2011) | Download Citation

Abstract

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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Acknowledgements

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.

Author information

Author notes

    • João M Dias
    •  & Ana I Kuehne

    These authors contributed equally to this work.

Affiliations

  1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.

    • João M Dias
    • , Dafna M Abelson
    • , Shridhar Bale
    • , Marnie L Fusco
    •  & Erica Ollmann Saphire
  2. Division of Virology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.

    • Ana I Kuehne
    • , Majidat A Muhammad
    • , Samantha E Zak
    • , Eugene Kang
    •  & John M Dye
  3. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.

    • Anthony C Wong
    •  & Kartik Chandran
  4. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.

    • Peter Halfmann
    •  & Yoshihiro Kawaoka
  5. Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

    • Yoshihiro Kawaoka
  6. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.

    • Erica Ollmann Saphire

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Contributions

J.M. Dias determined the crystal structure, S.B. continued refinement and M.L.F. engineered SUDV GP1,2 for crystallization. A.I.K., E.K., S.E.Z., M.A.M. and J.M. Dye raised 16F6 and designed and conducted BSL-4 neutralization and protection experiments. D.M.A., E.O.S., A.C.W. and K.C. designed and carried out cathepsin cleavage and VSIV neutralization experiments. D.M.A., E.O.S., P.H. and Y.K. designed and conducted attachment and entry experiments. J.M. Dias, J.M. Dye, D.M.A., S.B., A.K., K.C., P.H., Y.K. and E.O.S. analyzed results. J.M. Dye, K.C., Y.K. and E.O.S. supervised the research. J.M. Dias, J.M. Dye and E.O.S. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to John M Dye or Erica Ollmann Saphire.

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    Supplementary Figures 1–7, Supplementary Table 1 and Supplementary Methods

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DOI

https://doi.org/10.1038/nsmb.2150

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