IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-11256-z.html
   My bibliography  Save this article

Bypassing pan-enterovirus host factor PLA2G16

Author

Listed:
  • Jim Baggen

    (Utrecht University)

  • Yue Liu

    (Purdue University)

  • Heyrhyoung Lyoo

    (Utrecht University)

  • Arno L. W. Vliet

    (Utrecht University)

  • Maryam Wahedi

    (Utrecht University)

  • Jost W. Bruin

    (Utrecht University)

  • Richard W. Roberts

    (Utrecht University)

  • Pieter Overduin

    (Diagnostics and Screening, National Institute for Public Health and the Environment)

  • Adam Meijer

    (Diagnostics and Screening, National Institute for Public Health and the Environment)

  • Michael G. Rossmann

    (Purdue University)

  • Hendrik Jan Thibaut

    (Utrecht University)

  • Frank J. M. Kuppeveld

    (Utrecht University)

Abstract

Enteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we identify a possible mechanism of PLA2G16 evasion by employing a dual glycan receptor-binding enterovirus D68 (EV-D68) strain. We previously showed that this strain does not strictly require the canonical EV-D68 receptor sialic acid. Here, we employ a haploid screen to identify sulfated glycosaminoglycans (sGAGs) as its second glycan receptor. Remarkably, engagement of sGAGs enables this virus to bypass PLA2G16. Using cryo-EM analysis, we reveal that, in contrast to sialic acid, sGAGs stimulate genome release from virions via structural changes that enlarge the putative openings for genome egress. Together, we describe an enterovirus that can bypass PLA2G16 and identify additional virion destabilization as a potential mechanism to circumvent PLA2G16.

Suggested Citation

  • Jim Baggen & Yue Liu & Heyrhyoung Lyoo & Arno L. W. Vliet & Maryam Wahedi & Jost W. Bruin & Richard W. Roberts & Pieter Overduin & Adam Meijer & Michael G. Rossmann & Hendrik Jan Thibaut & Frank J. M., 2019. "Bypassing pan-enterovirus host factor PLA2G16," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11256-z
    DOI: 10.1038/s41467-019-11256-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-11256-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-11256-z?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
    ---><---

    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:10:y:2019:i:1:d:10.1038_s41467-019-11256-z. 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.