Copper-mediated MAM regulation of the NF-κB signalling pathway enhances Seneca Valley virus replication in PK-15...

Seneca Valley virus (SVV) is known to cause vesicular disease in swine, presenting new challenges to the pig industry. Recent studies have investigated the relationship between disrupted copper ion homeostasis and viral replication, suggesting that copper dysregulation has a significant impact on the replication of various viruses. Research has also shown that mitochondria-associated endoplasmic reticulum membrane (MAM) and NF-κB are involved in the innate immune response triggered by viral infections. However, the exact mechanisms by which copper (Cu), MAM, and NF-κB affect SVV replication remain unclear. In this study, it was found that SVV induces an imbalance in copper homeostasis, leading to dynamic changes in MAM while inhibiting the NF-κB pathway. This inhibition results in decreased levels of IL-6, IL-1β, TNF-α, IFN-α, and IFNλ3. Furthermore, the disruption of copper homeostasis in SVV-infected PK-15 cells regulates the NF-κB pathway through MAM, promoting SVV replication. This research provides valuable insights into the regulation of copper metabolism during SVV infection and establishes a theoretical framework for understanding the pathogenesis and immune activation mechanisms associated with SVV.