# Metabolic Imprint of Poliovirus on Glioblastoma Cells and Its Role in Virus Replication and Cytopathic Activity

## TL;DR

This study explores how poliovirus affects the metabolism of glioblastoma cells and how these changes influence virus replication and cell damage.

## Contribution

The study identifies specific metabolic pathways influenced by poliovirus in glioblastoma cells and evaluates potential drugs to enhance oncolytic effects.

## Key findings

- Poliovirus alters amino acid, purine, polyamine metabolism, mitochondrial respiration, and glycolysis in glioblastoma cells.
- 2-Deoxyglucose enhances the cytopathic effect of poliovirus, suggesting potential repurposing for oncolysis.
- Poliovirus replication is linked to mitochondrial network fragmentation, highlighting the role of mitochondria in viral activity.

## Abstract

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 H2O2, 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.