IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-09391-8.html
   My bibliography  Save this article

Structure mapping of dengue and Zika viruses reveals functional long-range interactions

Author

Listed:
  • Roland G. Huber

    (Bioinformatics Institute (A*STAR))

  • Xin Ni Lim

    (Genome Institute of Singapore)

  • Wy Ching Ng

    (Duke-NUS Graduate Medical School)

  • Adelene Y. L. Sim

    (Bioinformatics Institute (A*STAR))

  • Hui Xian Poh

    (Genome Institute of Singapore)

  • Yang Shen

    (Genome Institute of Singapore)

  • Su Ying Lim

    (Genome Institute of Singapore)

  • Karin B. Sundstrom

    (Duke-NUS Graduate Medical School)

  • Xuyang Sun

    (National Neuroscience Institute
    Genome Institute of Singapore)

  • Jong Ghut Aw

    (Genome Institute of Singapore)

  • Horng Khit Too

    (National University of Singapore
    National University of Singapore)

  • Peng Hee Boey

    (National University of Singapore
    National University of Singapore)

  • Andreas Wilm

    (Genome Institute of Singapore)

  • Tanu Chawla

    (Duke-NUS Graduate Medical School)

  • Milly M. Choy

    (Genome Institute of Singapore
    London School of Hygiene & Tropical Medicine)

  • Lu Jiang

    (A*STAR
    National University of Singapore)

  • Paola Florez Sessions

    (Genome Institute of Singapore)

  • Xian Jun Loh

    (A*STAR
    National University of Singapore)

  • Sylvie Alonso

    (National University of Singapore
    National University of Singapore)

  • Martin Hibberd

    (Genome Institute of Singapore
    London School of Hygiene & Tropical Medicine)

  • Niranjan Nagarajan

    (Genome Institute of Singapore)

  • Eng Eong Ooi

    (Duke-NUS Graduate Medical School
    National University of Singapore
    National University of Singapore)

  • Peter J. Bond

    (Bioinformatics Institute (A*STAR))

  • October M. Sessions

    (Duke-NUS Graduate Medical School
    National University of Singapore
    National University of Singapore)

  • Yue Wan

    (Genome Institute of Singapore
    Nanyang Technological University
    National University of Singapore)

Abstract

Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates. Interaction mapping by SPLASH identifies many pair-wise interactions, 40% of which form alternative structures, suggesting extensive structural heterogeneity. Analysis of shared interactions between serotypes reveals a conserved macro-organization whereby interactions can be preserved at physical locations beyond sequence identities. We further observe that longer-range interactions are preferentially disrupted inside cells, and show the importance of new interactions in virus fitness. These findings deepen our understanding of Flavivirus genome organization and serve as a resource for designing therapeutics in targeting RNA viruses.

Suggested Citation

  • Roland G. Huber & Xin Ni Lim & Wy Ching Ng & Adelene Y. L. Sim & Hui Xian Poh & Yang Shen & Su Ying Lim & Karin B. Sundstrom & Xuyang Sun & Jong Ghut Aw & Horng Khit Too & Peng Hee Boey & Andreas Wilm, 2019. "Structure mapping of dengue and Zika viruses reveals functional long-range interactions," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09391-8
    DOI: 10.1038/s41467-019-09391-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-09391-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-09391-8?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_s41467-019-09391-8. 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.