Influenza A Virus (H1N1) Infection Induces Ferroptosis to Promote Developmental Injury in Fetal Tissues

Abstract

H1N1, a globally pervasive subtype of influenza A virus (IAV), poses an ongoing threat to human health and occasionally leads to multi-organ dysfunction in severe cases. Evidence confirms that the H1N1 virus is enabled to penetrate the placental barrier; however, the underlying mechanisms by which maternal infection contributes to detrimental fetal outcomes remain elusive. In this study, a systematic literature review and meta-analysis demonstrated a strong association between maternal H1N1 infection during pregnancy and adverse fetal outcomes. Using a chicken embryo model, we found that the H1N1 virus specifically targets the developing liver and lung tissues, activates immune and stromal cells, and induces localised inflammatory responses, thereby triggering excessive oxidative stress. The resulting imbalance in oxidative stress disrupts antioxidant defence systems and promotes ferroptosis in parenchymal cells. Persistent ferroptosis subsequently initiates tissue repair processes, activates fibroblasts, and leads to aberrant extracellular matrix deposition, ultimately contributing to early fibrosis in the liver and lung tissues. Collectively, this study elucidates the molecular mechanisms by which H1N1 selectively infects fetal liver and lung, inducing ferroptosis-mediated parenchymal cell death and tissue fibrosis, thereby impairing fetal development. These findings provide novel theoretical insights for the clinical management and prevention of H1N1-associated maternal-fetal infections and adverse pregnancy outcomes.

Keywords

ferroptosis / fibrosis / H1N1 virus / maternal infection / oxidative stress

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