Induction of mitochondrial fission and mtDNA leakage via the Smad3/Drp1 axis by PEDV infection activates the TLR9/NF-κB/IL-1β inflammatory pathway

Abstract

Mitochondrial homeostasis is intricately linked to the pathogenesis of many viral infections. The maintenance of mitochondrial homeostasis and normal cellular functions relies heavily on the delicate balance of mitochondrial dynamics. However, the precise impact of porcine epidemic diarrhea virus (PEDV) infection on mitochondrial dynamics and subsequent pathological processes is largely unexplored. In this study, through both in vivo and in vitro infections, we have demonstrated that PEDV infection induces mitochondrial fission and leakage of mtDNA by upregulating Drp1 expression, and identified Smad3 as a crucial transcription factor responsible for regulating Drp1 expression. By establishing an inflammatory model using PEDV-infected cells, we have identified Drp1-mediated mtDNA release as an upstream event triggering TLR9/NF-κB pathway activation during PEDV infection. These findings provide novel insights into the relationship between PEDV infection and host inflammatory responses from the perspective of mitochondrial dynamics.