IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15844-2.html
   My bibliography  Save this article

The UPR sensor IRE1α and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections

Author

Listed:
  • Vibhu Prasad

    (University of Zurich)

  • Maarit Suomalainen

    (University of Zurich)

  • Yllza Jasiqi

    (University of Zurich)

  • Silvio Hemmi

    (University of Zurich)

  • Patrick Hearing

    (Stony Brook University)

  • Louise Hosie

    (University of Warwick, School of Life Sciences
    The Francis Crick Institute)

  • Hans-Gerhard Burgert

    (University of Warwick, School of Life Sciences
    Institute of Virology, University Medical Center Freiburg)

  • Urs F. Greber

    (University of Zurich)

Abstract

Persistent viruses cause chronic disease, and threaten the lives of immunosuppressed individuals. Here, we elucidate a mechanism supporting the persistence of human adenovirus (AdV), a virus that can kill immunosuppressed patients. Cell biological analyses, genetics and chemical interference demonstrate that one of five AdV membrane proteins, the E3-19K glycoprotein specifically triggers the unfolded protein response (UPR) sensor IRE1α in the endoplasmic reticulum (ER), but not other UPR sensors, such as protein kinase R-like ER kinase (PERK) and activating transcription factor 6 (ATF6). The E3-19K lumenal domain activates the IRE1α nuclease, which initiates mRNA splicing of X-box binding protein-1 (XBP1). XBP1s binds to the viral E1A-enhancer/promoter sequence, and boosts E1A transcription, E3-19K levels and lytic infection. Inhibition of IRE1α nuclease interrupts the five components feedforward loop, E1A, E3-19K, IRE1α, XBP1s, E1A enhancer/promoter. This loop sustains persistent infection in the presence of the immune activator interferon, and lytic infection in the absence of interferon.

Suggested Citation

  • Vibhu Prasad & Maarit Suomalainen & Yllza Jasiqi & Silvio Hemmi & Patrick Hearing & Louise Hosie & Hans-Gerhard Burgert & Urs F. Greber, 2020. "The UPR sensor IRE1α and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15844-2
    DOI: 10.1038/s41467-020-15844-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15844-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-15844-2?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:11:y:2020:i:1:d:10.1038_s41467-020-15844-2. 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.