IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42545-3.html
   My bibliography  Save this article

IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma

Author

Listed:
  • Xueqin Chen

    (Jinan University
    Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine)

  • Jun Liu

    (Jinan University)

  • Yuqin Li

    (Jinan University)

  • Yuequan Zeng

    (Jinan University)

  • Fang Wang

    (Jinan University)

  • Zexiong Cheng

    (Jinan University)

  • Hao Duan

    (Sun Yat-sen University Cancer Center)

  • Guopeng Pan

    (Jinan University)

  • Shangqi Yang

    (Jinan University)

  • Yuling Chen

    (Fudan University
    Fudan University)

  • Qing Li

    (Jinan University)

  • Xi Shen

    (Jinan University)

  • Ying Li

    (Jinan University)

  • Zixi Qin

    (Jinan University)

  • Jiahong Chen

    (Jinan University
    Peking University)

  • Youwei Huang

    (Jinan University)

  • Xiangyu Wang

    (Jinan University)

  • Yuli Lu

    (Jinan University
    Shantou Centre for Disease Control and Prevention)

  • Minfeng Shu

    (Fudan University
    Fudan University)

  • Yubo Zhang

    (Jinan University)

  • Guocai Wang

    (Jinan University)

  • Kai Li

    (The Sixth Affiliated Hospital of Sun Yat-sen University)

  • Xi Lin

    (Jinan University)

  • Fan Xing

    (Southern Medical University)

  • Haipeng Zhang

    (Jinan University
    Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education)

Abstract

IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known regarding its regulation in antiviral immunity. Here, we discover that IDH1 mutation inhibits virus-induced interferon (IFN) antiviral responses in glioma cells. Mechanistically, D2HG produced by mutant IDH1 enhances the binding of DNMT1 to IRF3/7 promoters such that IRF3/7 are downregulated, leading to impaired type I IFN response in glioma cells, which enhances the susceptibility of gliomas to viral infection. Furthermore, we identify DNMT1 as a potential biomarker predicting which IDH1mut gliomas are most likely to respond to oncolytic virus. Finally, both D2HG and ectopic mutant IDH1 can potentiate the replication and oncolytic efficacy of VSVΔ51 in female mouse models. These findings reveal a pivotal role for IDH1 mutation in regulating antiviral response and demonstrate that IDH1 mutation confers sensitivity to oncolytic virotherapy.

Suggested Citation

  • Xueqin Chen & Jun Liu & Yuqin Li & Yuequan Zeng & Fang Wang & Zexiong Cheng & Hao Duan & Guopeng Pan & Shangqi Yang & Yuling Chen & Qing Li & Xi Shen & Ying Li & Zixi Qin & Jiahong Chen & Youwei Huang, 2023. "IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42545-3
    DOI: 10.1038/s41467-023-42545-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42545-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42545-3?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:14:y:2023:i:1:d:10.1038_s41467-023-42545-3. 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.