Zenov Martin A, Yanvarev Dmitry V, Ivanova Olga N, Denisova Ekaterina A, Golikov Mikhail V, Fedulov Artemy P, Frykin Roman I, Sarkisova Viktoria A, Goldstein Dmitry A, Chumakov Peter M, Lipatova Anastasia V, Ivanov Alexander V
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Int J Mol Sci. 2025 Jul 30;26(15):7346. doi: 10.3390/ijms26157346.
Poliovirus represents an oncolytic agent for human glioblastoma-one of the most aggressive types of cancer. Since interference of viruses with metabolic and redox pathways is often linked to their pathogenesis, drugs targeting metabolic enzymes are regarded as potential enhancers of oncolysis. Our goal was to reveal an imprint of poliovirus on the metabolism of glioblastoma cell lines and to assess the dependence of the virus on these pathways. Using GC-MS, HPLC, and Seahorse techniques, we show that poliovirus interferes with amino acid, purine and polyamine metabolism, mitochondrial respiration, and glycolysis. However, many of these changes are cell line- and culture medium-dependent. 2-Deoxyglucose, the pharmacologic inhibitor of glycolysis, was shown to enhance the cytopathic effect of poliovirus, pointing to its possible repurposing as an enhancer of oncolysis. Inhibitors of polyamine biosynthesis, pyruvate import into mitochondria, and fatty acid oxidation exhibited antiviral activity, albeit in a cell-dependent manner. We also demonstrate that poliovirus does not interfere with the production of superoxide anions or with levels of HO, showing an absence of oxidative stress during infection. Finally, we showed that a high rate of poliovirus replication is associated with fragmentation of the mitochondrial network, pointing to the significance of these organelles for the virus.
脊髓灰质炎病毒是一种用于治疗人类胶质母细胞瘤的溶瘤剂，胶质母细胞瘤是最具侵袭性的癌症类型之一。由于病毒对代谢和氧化还原途径的干扰通常与其发病机制相关，靶向代谢酶的药物被视为溶瘤作用的潜在增强剂。我们的目标是揭示脊髓灰质炎病毒对胶质母细胞瘤细胞系代谢的影响，并评估病毒对这些途径的依赖性。使用气相色谱 - 质谱联用仪（GC-MS）、高效液相色谱（HPLC）和海马技术，我们发现脊髓灰质炎病毒会干扰氨基酸、嘌呤和多胺代谢、线粒体呼吸以及糖酵解。然而，其中许多变化取决于细胞系和培养基。糖酵解的药理抑制剂2-脱氧葡萄糖被证明可增强脊髓灰质炎病毒的细胞病变效应，这表明它可能被重新用作溶瘤增强剂。多胺生物合成抑制剂、丙酮酸导入线粒体的抑制剂以及脂肪酸氧化抑制剂均表现出抗病毒活性，尽管其活性具有细胞依赖性。我们还证明脊髓灰质炎病毒不会干扰超氧阴离子的产生或过氧化氢（HO）的水平，表明感染过程中不存在氧化应激。最后，我们表明脊髓灰质炎病毒的高复制率与线粒体网络的碎片化有关，这表明这些细胞器对病毒具有重要意义。
