IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01708-9.html
   My bibliography  Save this article

Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein

Author

Listed:
  • Michael B. Battles

    (Geisel School of Medicine at Dartmouth)

  • Vicente Más

    (Unidad de Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Eduardo Olmedillas

    (Unidad de Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Olga Cano

    (Unidad de Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Mónica Vázquez

    (Unidad de Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Laura Rodríguez

    (Unidad de Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III
    University of Rochester Medical Center)

  • José A. Melero

    (Unidad de Biología Viral, Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III)

  • Jason S. McLellan

    (Geisel School of Medicine at Dartmouth)

Abstract

Human metapneumovirus (hMPV) is a frequent cause of bronchiolitis in young children. Its F glycoprotein mediates virus–cell membrane fusion and is the primary target of neutralizing antibodies. The inability to produce recombinant hMPV F glycoprotein in the metastable pre-fusion conformation has hindered structural and immunological studies. Here, we engineer a pre-fusion-stabilized hMPV F ectodomain and determine its crystal structure to 2.6 Å resolution. This structure reveals molecular determinants of strain-dependent acid-induced fusion, as well as insights into refolding from pre- to post-fusion conformations. A dense glycan shield at the apex of pre-fusion hMPV F suggests that antibodies against this site may not be elicited by host immune responses, which is confirmed by depletion studies of human immunoglobulins and by mouse immunizations. This is a major difference with pre-fusion F from human respiratory syncytial virus (hRSV), and collectively our results should facilitate development of effective hMPV vaccine candidates.

Suggested Citation

  • Michael B. Battles & Vicente Más & Eduardo Olmedillas & Olga Cano & Mónica Vázquez & Laura Rodríguez & José A. Melero & Jason S. McLellan, 2017. "Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01708-9
    DOI: 10.1038/s41467-017-01708-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01708-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01708-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Karen J. Gonzalez & Jiachen Huang & Miria F. Criado & Avik Banerjee & Stephen M. Tompkins & Jarrod J. Mousa & Eva-Maria Strauch, 2024. "A general computational design strategy for stabilizing viral class I fusion proteins," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Ching-Lin Hsieh & Scott A. Rush & Concepcion Palomo & Chia-Wei Chou & Whitney Pickens & Vicente Más & Jason S. McLellan, 2022. "Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Xiao Xiao & Arthur Fridman & Lu Zhang & Pavlo Pristatsky & Eberhard Durr & Michael Minnier & Aimin Tang & Kara S. Cox & Zhiyun Wen & Renee Moore & Dongrui Tian & Jennifer D. Galli & Scott Cosmi & Mich, 2022. "Profiling of hMPV F-specific antibodies isolated from human memory B cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Madelyn Cabán & Justas V. Rodarte & Madeleine Bibby & Matthew D. Gray & Justin J. Taylor & Marie Pancera & Jim Boonyaratanakornkit, 2023. "Cross-protective antibodies against common endemic respiratory viruses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01708-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.