Wu Xiaoli, Zhu Song, Li Min, Xu Zhiwen, Zhu Ling, Deng Junliang, Deng Huidan
College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China.
Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China.
Vet Res. 2025 Sep 19;56(1):175. doi: 10.1186/s13567-025-01578-w.
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.
已知塞内卡山谷病毒（SVV）可引起猪的水疱性疾病，给养猪业带来了新的挑战。最近的研究调查了铜离子稳态破坏与病毒复制之间的关系，表明铜失调对多种病毒的复制有重大影响。研究还表明，线粒体相关内质网膜（MAM）和核因子κB（NF-κB）参与了病毒感染引发的先天免疫反应。然而，铜（Cu）、MAM和NF-κB影响SVV复制的确切机制仍不清楚。在本研究中，发现SVV诱导铜稳态失衡，导致MAM发生动态变化，同时抑制NF-κB途径。这种抑制导致白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、干扰素-α（IFN-α）和干扰素λ3（IFNλ3）水平降低。此外，SVV感染的PK-15细胞中铜稳态的破坏通过MAM调节NF-κB途径，促进SVV复制。本研究为深入了解SVV感染期间铜代谢的调节提供了有价值的见解，并为理解与SVV相关的发病机制和免疫激活机制建立了理论框架。
