Moderate Metabolic Changes Are Dispensable for Replication and Oncolytic Activity of Poliovirus in Glioblastoma Cells

Poliovirus represents an oncolytic agent 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 imprint of poliovirus on metabolism of glioblastoma cells lines and to assess 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. Inhibitors of metabolic enzymes affected neither poliovirus replication nor cytopathogenic effect with the exception of inhibitors of polyamine biosynthesis and pyruvate import into mitochondria that exhibited antiviral activity. We also demonstrate that poliovirus does not interfere with production of superoxide anions or with levels of H2O2 showing absence of oxidative stress during the infection. So, poliovirus pathogenesis is not associated with alterations of cell metabolism or redox status, and pharmacological inhibitors of metabolic enzymes cannot be used to boost its oncolytic activity.