Validation of important genes and bioinformatics investigation of the relationship between ferroptosis and CVA16 infection.

Coxsackievirus A16 (CVA16) is a major pathogen linked to hand, foot, and mouth disease (HFMD), and effective therapies and vaccines are lacking. Ferroptosis, an iron-dependent form of cell death, may play a role in CVA16 infection and remains underexplored. We analyzed microarray datasets (GSE71673) from the Gene Expression Omnibus (GEO) and ferroptosis-related genes (FRGs) from FerrDb. A Venn diagram revealed 37 ferroptosis-related differentially expressed genes (FR-DEGs), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on these genes. Protein-protein interaction (PPI) analysis revealed seven hub genes, and five hub genes were validated in CVA16-infected U251 cells via quantitative reverse transcription polymerase chain reaction (qRT-PCR). We constructed various interaction networks via the Network Analyst platform, revealing complex relationships between FR-DEGs. This study enhances the understanding of the molecular mechanisms linking ferroptosis and CVA16 infection, offering insights and therapeutic targets for its prevention and treatment.