IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26910-8.html
   My bibliography  Save this article

SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis

Author

Listed:
  • Ji-Seung Yoo

    (Hokkaido University Graduate School of Medicine)

  • Michihito Sasaki

    (Hokkaido University)

  • Steven X. Cho

    (Hokkaido University Graduate School of Medicine)

  • Yusuke Kasuga

    (Hokkaido University Graduate School of Medicine)

  • Baohui Zhu

    (Hokkaido University Graduate School of Medicine)

  • Ryota Ouda

    (Hokkaido University Graduate School of Medicine)

  • Yasuko Orba

    (Hokkaido University
    Hokkaido University)

  • Paul Figueiredo

    (Texas A&M University
    Texas A&M Health Science Center)

  • Hirofumi Sawa

    (Hokkaido University
    Hokkaido University
    Hokkaido University)

  • Koichi S. Kobayashi

    (Hokkaido University Graduate School of Medicine
    Texas A&M Health Science Center)

Abstract

The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5.

Suggested Citation

  • Ji-Seung Yoo & Michihito Sasaki & Steven X. Cho & Yusuke Kasuga & Baohui Zhu & Ryota Ouda & Yasuko Orba & Paul Figueiredo & Hirofumi Sawa & Koichi S. Kobayashi, 2021. "SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26910-8
    DOI: 10.1038/s41467-021-26910-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26910-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26910-8?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
    ---><---

    Citations

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


    Cited by:

    1. Srikanth Sadhu & Rajdeep Dalal & Jyotsna Dandotiya & Akshay Binayke & Virendra Singh & Manas Ranjan Tripathy & Vinayaka Das & Sandeep Goswami & Shakti Kumar & Zaigham Abbas Rizvi & Amit Awasthi, 2023. "IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation," Nature Communications, Nature, vol. 14(1), pages 1-16, 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:12:y:2021:i:1:d:10.1038_s41467-021-26910-8. 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.