IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
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Published:2023-10-25
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Chen Xueqin, Liu JunORCID, Li Yuqin, Zeng Yuequan, Wang Fang, Cheng Zexiong, Duan HaoORCID, Pan Guopeng, Yang Shangqi, Chen Yuling, Li Qing, Shen Xi, Li Ying, Qin Zixi, Chen Jiahong, Huang Youwei, Wang Xiangyu, Lu Yuli, Shu MinfengORCID, Zhang Yubo, Wang Guocai, Li Kai, Lin Xi, Xing Fan, Zhang HaipengORCID
Abstract
AbstractIDH1 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.
Funder
National Natural Science Foundation of China Pearl River S and T Nova Program of Guangzhou Guangdong Natural Science Funds of Distinguished Young Scholar
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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