Semenov Dmitriy V, Vasileva Natalia S, Menyailo Maxim E, Mishinov Sergey V, Savinovskaya Yulya I, Ageenko Alisa B, Chesnokova Anna S, Dymova Maya A, Stepanov Grigory A, Kochneva Galina V, Richter Vladimir A, Kuligina Elena V
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentyev Avenue, 8, Novosibirsk 630090, Russia.
Sirius University of Science and Technology, Sirius (Federal Territory of Sirius) 354340, Krasnodar Region, Russia.
Int J Mol Sci. 2025 Jul 20;26(14):6983. doi: 10.3390/ijms26146983.
Oncolytic virotherapy is a rapidly evolving approach to cancer treatment. Our group previously designed VV-GMCSF-Lact, a recombinant oncolytic vaccinia virus targeting solid tumors including gliomas. In this study, we used single-cell RNA sequencing to compare transcriptional responses in human glioma cells, non-malignant brain cells, and immortalized glioblastoma U87 MG cells following infection with this oncolytic virus. We found that proneural glioblastoma cells and microglia-like cells from patient-derived glioma cultures were the most susceptible to VV-GMCSF-Lact. Increased expressions of histones, translational regulators, and ribosomal proteins positively correlated with viral load at the transcript level. Furthermore, higher viral loads were accompanied by a large-scale downregulation of genes involved in mitochondrial translation, metabolism, and oxidative phosphorylation. Levels of early vaccinia virus transcripts are also positively correlated with infection intensity, suggesting that the fate of cells is determined at the early stage of infection.
溶瘤病毒疗法是一种快速发展的癌症治疗方法。我们的团队之前设计了VV-GMCSF-Lact，一种靶向包括神经胶质瘤在内的实体瘤的重组溶瘤痘苗病毒。在这项研究中，我们使用单细胞RNA测序来比较人神经胶质瘤细胞、非恶性脑细胞和永生化胶质母细胞瘤U87 MG细胞在感染这种溶瘤病毒后的转录反应。我们发现，来自患者来源的神经胶质瘤培养物中的神经干细胞样胶质母细胞瘤细胞和小胶质细胞样细胞对VV-GMCSF-Lact最敏感。组蛋白、翻译调节因子和核糖体蛋白的表达增加与转录水平上的病毒载量呈正相关。此外，较高的病毒载量伴随着参与线粒体翻译、代谢和氧化磷酸化的基因的大规模下调。早期痘苗病毒转录本的水平也与感染强度呈正相关，这表明细胞的命运在感染早期就已确定。
