Single-Cell Transcriptomic Changes in Patient-Derived Glioma and U87 Glioblastoma Cell Cultures Infected with the Oncolytic Virus VV-GMCSF-Lact
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.
Authors
- Г. А. Степанов (ORCID: https://orcid.org/0000-0003-3393-3192)
- Yulya I. Savinovskaya
- Vladimir A. Richter (ORCID: https://orcid.org/0000-0001-5849-5892)
- Г. В. Кочнева (ORCID: https://orcid.org/0000-0002-2420-0483)
- Natalia Vasileva (ORCID: https://orcid.org/0000-0002-0392-794X)
- Alisa Ageenko (ORCID: https://orcid.org/0000-0002-6909-7301)
- Maxim E. Menyailo (ORCID: https://orcid.org/0000-0003-4630-4934)
- М. А. Дымова (ORCID: https://orcid.org/0000-0002-7281-9096)
- С. В. Мишинов (ORCID: https://orcid.org/0000-0002-0903-7278)
- Elena V. Kuligina (ORCID: https://orcid.org/0000-0003-3145-1878)
- Dmitriy Semenov
Institutions
- Russian Academy of Sciences (RU)
- State Research Center of Virology and Biotechnology VECTOR (RU)
- Institute of Chemical Biology and Fundamental Medicine (RU)
- Sirius University of Science and Technology (RU)
- Tomsk National Research Medical Center (RU)
- Siberian Branch of the Russian Academy of Sciences (RU)
- Novosibirsk Scientific Research Institute of Traumatology and Orthopedics. Ya.L. Tsivyan (RU)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-07-20
- DOI
- https://doi.org/10.3390/ijms26146983
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Russian Science Foundation