Dynamic Changes in ACSL4 Following Influenza A/H1N1, A/H3N2, and Influenza B Infection

Abstract

Context: Ferroptosis is an understudied iron-dependent cell death pathway characterized by lipid peroxidation and has emerged as a critical mediator of virus-induced cytotoxicity and inflammation, particularly in respiratory viral infections. Objectives: This study examined the temporal regulation of ACSL4, a key pro-ferroptotic enzyme. Evidence Acquisition: A549 cells were infected with influenza A/H1N1, influenza A/H3N2, and influenza B viruses and assessed at 24 and 48 hours post-infection (hpi). ACSL4 expression was evaluated using quantitative reverse transcription-polymerase chain reaction, followed by post hoc analysis. Results: ACSL4 expression showed modest changes at 48 hpi in the A/H1N1 and A/H3N2 groups. However, a pronounced upregulation was observed at 24 hpi, particularly in the A/H1N1 group, with a log fold change increase of 1.52 (P = 0.005). The greatest downregulation was observed at 48 hpi in the influenza B group, with a significant log fold change of -4.11. Conclusions: These findings indicate the time-dependent activation of pro-ferroptotic mRNA associated with ferroptosis during influenza virus infection and suggest that ACSL4 may be a mediator of virus-induced cell death and a target for antiviral interventions.