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

doi:10.1038/s41467-023-42545-3

Cited by 6 publications

(3 citation statements)

References 39 publications

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“…Mammals have three IDH subtypes: mitochondrial NAD-IDH (IDH3), mitochondrial NADP-IDH (IDH2), and cytoplasmic NADP-IDH (IDH1) ( Chen and Ding, 2023 ). The IDH1 mutation inhibits the virus-induced IFN antiviral response in glioma cells ( Chen et al, 2023 ). IDH2 particles respond to oxidative injury and regulate lipogenesis and glycolysis ( Filipp et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of host proteins interacting with the E protein of porcine epidemic diarrhea virus

Qiu,

Sun,

Zheng

et al. 2024

Front. Microbiol.

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IntroductionPorcine epidemic diarrhea (PED) is an acute, highly contagious, and high-mortality enterophilic infectious disease caused by the porcine epidemic diarrhea virus (PEDV). PEDV is globally endemic and causes substantial economic losses in the swine industry. The PEDV E protein is the smallest structural protein with high expression levels that interacts with the M protein and participates in virus assembly. However, how the host proteins interact with E proteins in PEDV replication remains unknown.MethodsWe identified host proteins that interact with the PEDV E protein using a combination of PEDV E protein-labeled antibody co-immunoprecipitation and tandem liquid-chromatography mass-spectroscopy (LC-MS/MS).ResultsBioinformatical analysis showed that in eukaryotes, ribosome biogenesis, RNA transport, and amino acid biosynthesis represent the three main pathways that are associated with the E protein. The interaction between the E protein and isocitrate dehydrogenase [NAD] β-subunit (NAD-IDH-β), DNA-directed RNA polymerase II subunit RPB9, and mRNA-associated protein MRNP 41 was validated using co-immunoprecipitation and confocal assays. NAD-IDH-β overexpression significantly inhibited viral replication.DiscussionThe antiviral effect of NAD-IDH-β suggesting that the E protein may regulate host metabolism by interacting with NAD-IDH-β, thereby reducing the available energy for viral replication. Elucidating the interaction between the PEDV E protein and host proteins may clarify its role in viral replication. These results provide a theoretical basis for the study of PEDV infection mechanism and antiviral targets.

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Section: Discussionmentioning

confidence: 99%

Identification of host proteins interacting with the E protein of porcine epidemic diarrhea virus

Qiu,

Sun,

Zheng

et al. 2024

Front. Microbiol.

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“…A global study of mutations in viral replication is important to understand viral evolution and drug resistance [ 34 ], disease pathogenesis [ 35 ] and the development of antiviral strategies [ 36 ]. These studies provide insights and knowledge into the molecular mechanisms underlying viral replication at the population level and offer a foundation for the development of targeted therapeutic interventions and the design of novel antiviral agents [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Bio-Chemoinformatics-Driven Analysis of nsp7 and nsp8 Mutations and Their Effects on Viral Replication Protein Complex Stability

Subong,

Ozawa

2024

CIMB

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The nonstructural proteins 7 and 8 (nsp7 and nsp8) of SARS-CoV-2 are highly important proteins involved in the RNA-dependent polymerase (RdRp) protein replication complex. In this study, we analyzed the global mutation of nsp7 and nsp8 in 2022 and 2023 and analyzed the effects of mutation on the viral replication protein complex using bio-chemoinformatics. Frequently occurring variants are found to be single amino acid mutations for both nsp7 and nsp8. The most frequently occurring mutations for nsp7 which include L56F, L71F, S25L, M3I, D77N, V33I and T83I are predicted to cause destabilizing effects, whereas those in nsp8 are predicted to cause stabilizing effects, with the threonine to isoleucine mutation (T89I, T145I, T123I, T148I, T187I) being a frequent mutation. A conserved domain database analysis generated critical interaction residues for nsp7 (Lys-7, His-36 and Asn-37) and nsp8 (Lys-58, Pro-183 and Arg-190), which, according to thermodynamic calculations, are prone to destabilization. Trp-29, Phe-49 of nsp7 and Trp-154, Tyr-135 and Phe-15 of nsp8 cause greater destabilizing effects to the protein complex based on a computational alanine scan suggesting them as possible new target sites. This study provides an intensive analysis of the mutations of nsp7 and nsp8 and their possible implications for viral complex stability.

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“…Its ability to bypass the BBB through intratumoral inoculation enables direct infection and lysis of tumor cells. This, in turn, reverses tumor immune escape, enhances the cross-presentation of tumor antigens, and enhances the immune system resisting tumors [ 662 , 668 , 669 ].…”

Section: Current Treatment Strategies and Progress Of Glioblastomamentioning

confidence: 99%

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

Lin,

Liu,

et al. 2024

J Hematol Oncol

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Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4–8%) of CD45+ cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.

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IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma

Cited by 6 publications

References 39 publications

Identification of host proteins interacting with the E protein of porcine epidemic diarrhea virus

Identification of host proteins interacting with the E protein of porcine epidemic diarrhea virus

Bio-Chemoinformatics-Driven Analysis of nsp7 and nsp8 Mutations and Their Effects on Viral Replication Protein Complex Stability

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

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