CVA6 could cause pathogenesis in the ICR mouse brain tissues and the human glioma (U251) cells to the detailed dysregulated genes with notable features showing upregulation of antiviral and immune response-related genes such as Zbp1, Usp18, Oas2, Irf7, Ddx60, Ifit3, Ddx58, and Isg15, while downregulating neurological system process-related genes, such as Fcrls, Ebnrb, Cdk1, and Anxa5. Here, ISG15 is linked to central nervous system cancer.