HIF-1α stabilization inhibits Japanese encephalitis virus propagation and neurotoxicity via autophagy pathways

Japanese encephalitis (JE) is a widespread flavivirus that induces brain inflammation and affects the central nervous system (CNS). Deferoxamine, an iron chelator, has shown promising results in stabilizing HIF-1α, a protein that improves hypoxic conditions, offers protective effects against neurological, and neurodegenerative diseases. This study aimed to assess the impact of HIF-1α stabilization during JEV infection using SH-SY5Y neuroblastoma cell lines as a model. Our findings demonstrated that deferoxamine treatment increased HIF-1α protein levels, leading to a reduction in JEV propagation. Moreover, RT-PCR analysis revealed that deferoxamine ameliorated JEV-induced neuroinflammation and neurotoxicity. We proved that inducing HIF-1α is essential for having an impact of deferoxamine against JEV-mediated neurotoxicity. Thus, our findings offer a potential therapeutic approach to mitigate the detrimental effects of JEV infection on neuronal cells. Further investigations also demonstrated that deferoxamine could reverse JEV-induced autophagy inhibition by stabilizing HIF-1α, which plays a crucial role in mitigating neuronal cell damage and neuroinflammation. Based on our data, HIF-1α stabilization emerges as a vital factor against JEV infection in the neurons, highlighting deferoxamine as a promising and innovative target for developing anti-JEV agents.