Abstract
Epidemic encephalitis B caused by Japanese encephalitis virus (JEV) is a common zoonotic disease that poses threats to both pigs and humans. The cellular defense mechanism is closely tied to the body's resistance to viral invasion. Regulated cell death, such as ferroptosis, is a strategy employed by host cells to defend against viral invasions. To understand the effect of ferroptosis on the proliferation of JEV, experimentally infected PK15 cells were treated with a ferroptosis agonist or antagonist. The results indicated that the ferroptosis agonist can suppress JEV proliferation, whereas the ferroptosis antagonist promotes JEV proliferation. Functional enrichment analysis showed that the ferroptosis agonist Erastin and antagonist SP600125 could affect JEV proliferation through the TNF, IL-17, Toll-like receptor, PI3K-AKT, and chemokine signaling pathways, as well as ECM-receptor interactions. Combined transcriptome and proteome analyses revealed 31 important genes, which are significantly associated with ferroptosis and the inflammatory response. Our results provide a better understanding of the molecular mechanisms through which ferroptosis affects the proliferation of JEV.