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IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma

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 r...

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Autores principales: Chen, Xueqin, Liu, Jun, Li, Yuqin, Zeng, Yuequan, Wang, Fang, Cheng, Zexiong, Duan, Hao, Pan, Guopeng, Yang, Shangqi, Chen, Yuling, Li, Qing, Shen, Xi, Li, Ying, Qin, Zixi, Chen, Jiahong, Huang, Youwei, Wang, Xiangyu, Lu, Yuli, Shu, Minfeng, Zhang, Yubo, Wang, Guocai, Li, Kai, Lin, Xi, Xing, Fan, Zhang, Haipeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600173/
https://www.ncbi.nlm.nih.gov/pubmed/37880243
http://dx.doi.org/10.1038/s41467-023-42545-3
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author Chen, Xueqin
Liu, Jun
Li, Yuqin
Zeng, Yuequan
Wang, Fang
Cheng, Zexiong
Duan, Hao
Pan, Guopeng
Yang, Shangqi
Chen, Yuling
Li, Qing
Shen, Xi
Li, Ying
Qin, Zixi
Chen, Jiahong
Huang, Youwei
Wang, Xiangyu
Lu, Yuli
Shu, Minfeng
Zhang, Yubo
Wang, Guocai
Li, Kai
Lin, Xi
Xing, Fan
Zhang, Haipeng
author_facet Chen, Xueqin
Liu, Jun
Li, Yuqin
Zeng, Yuequan
Wang, Fang
Cheng, Zexiong
Duan, Hao
Pan, Guopeng
Yang, Shangqi
Chen, Yuling
Li, Qing
Shen, Xi
Li, Ying
Qin, Zixi
Chen, Jiahong
Huang, Youwei
Wang, Xiangyu
Lu, Yuli
Shu, Minfeng
Zhang, Yubo
Wang, Guocai
Li, Kai
Lin, Xi
Xing, Fan
Zhang, Haipeng
author_sort Chen, Xueqin
collection PubMed
description 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.
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spelling pubmed-106001732023-10-27 IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma Chen, Xueqin Liu, Jun Li, Yuqin Zeng, Yuequan Wang, Fang Cheng, Zexiong Duan, Hao Pan, Guopeng Yang, Shangqi Chen, Yuling Li, Qing Shen, Xi Li, Ying Qin, Zixi Chen, Jiahong Huang, Youwei Wang, Xiangyu Lu, Yuli Shu, Minfeng Zhang, Yubo Wang, Guocai Li, Kai Lin, Xi Xing, Fan Zhang, Haipeng Nat Commun Article 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. Nature Publishing Group UK 2023-10-25 /pmc/articles/PMC10600173/ /pubmed/37880243 http://dx.doi.org/10.1038/s41467-023-42545-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Xueqin
Liu, Jun
Li, Yuqin
Zeng, Yuequan
Wang, Fang
Cheng, Zexiong
Duan, Hao
Pan, Guopeng
Yang, Shangqi
Chen, Yuling
Li, Qing
Shen, Xi
Li, Ying
Qin, Zixi
Chen, Jiahong
Huang, Youwei
Wang, Xiangyu
Lu, Yuli
Shu, Minfeng
Zhang, Yubo
Wang, Guocai
Li, Kai
Lin, Xi
Xing, Fan
Zhang, Haipeng
IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
title IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
title_full IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
title_fullStr IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
title_full_unstemmed IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
title_short IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
title_sort idh1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600173/
https://www.ncbi.nlm.nih.gov/pubmed/37880243
http://dx.doi.org/10.1038/s41467-023-42545-3
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