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Structure of the human metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site

Nature Structural & Molecular Biology volume 19, pages 461463 (2012) | Download Citation

Abstract

Human metapneumovirus and respiratory syncytial virus cause lower respiratory tract infections. The virus fusion (F) glycoprotein promotes membrane fusion by refolding from a metastable pre-fusion to a stable post-fusion conformation. F is also a major target of the neutralizing antibody response. Here we show that a potently neutralizing anti–human metapneumovirus antibody (DS7) binds a structurally invariant domain of F, revealing a new epitope that could be targeted in vaccine development.

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Acknowledgements

We thank past and present members of the Jardetzky, Crowe, Williams and Lamb laboratories. This research was supported in part by US National Institutes of Health research grants to J.V.W. (AI-085062, AI-073697 and AI-072414), R.A.L. (AI-23173) and T.S.J. (GM-61050). R.A.L. is an investigator of the Howard Hughes Medical Institute. J.E.C. is a Burroughs Wellcome Fund Clinical Scientist in Translational Research.

Author information

Affiliations

  1. Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA.

    • Xiaolin Wen
    •  & Theodore S Jardetzky
  2. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Jens C Krause
    • , John V Williams
    •  & James E Crowe Jr
  3. Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.

    • Jens C Krause
    • , John V Williams
    •  & James E Crowe Jr
  4. Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois, USA.

    • George P Leser
    •  & Robert A Lamb
  5. Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.

    • George P Leser
    •  & Robert A Lamb
  6. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Reagan G Cox
    • , John V Williams
    •  & James E Crowe Jr

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Contributions

X.W., J.C.K., G.P.L., R.G.C., R.A.L., J.V.W., J.E.C. and T.S.J. designed experiments and reagents. X.W., J.C.K., G.P.L., R.G.C. and T.S.J. conducted experiments and contributed reagents. X.W., G.P.L. and T.S.J. wrote the manuscript and Supplementary information and prepared the figures. X.W., J.C.K., G.P.L., R.G.C., R.A.L., J.V.W., J.E.C. and T.S.J. analyzed data and edited the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Theodore S Jardetzky.

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    Supplementary Figures 1–3, Supplementary Tables 1–4 and Supplementary Discussion

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DOI

https://doi.org/10.1038/nsmb.2250

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