College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Vet Res. 2024 Sep 27;55(1):115. doi: 10.1186/s13567-024-01370-2.
Senecavirus A (SVA), an emerging virus that causes blisters on the nose and hooves, reduces the production performance of pigs. RSAD2 is a radical S-adenosylmethionine (SAM) enzyme, and its expression can suppress various viruses due to its broad antiviral activity. However, the regulatory relationship between SVA and RSAD2 and the mechanism of action remain unclear. Here, we demonstrated that SVA infection increased RSAD2 mRNA levels, whereas RSAD2 expression negatively regulated viral replication, as evidenced by decreased viral VP1 protein expression, viral titres, and infected cell numbers. Viral proteins that interact with RSAD2 were screened, and the interaction between the 2 C protein and RSAD2 was found to be stronger than that between other proteins. Additionally, amino acids (aa) 43-70 of RSAD2 were crucial for interacting with the 2 C protein and played an important role in its anti-SVA activity. RSAD2 was induced by type I interferon (IFN-I) via Janus kinase signal transducer and activator of transcription (JAK-STAT), and had antiviral activity. Ruxolitinib, a JAK-STAT pathway inhibitor, and the knockdown of JAK1 expression substantially reduced RSAD2 expression levels and antiviral activity. Taken together, these results revealed that RSAD2 blocked SVA infection by interacting with the viral 2 C protein and provide a strategy for preventing and controlling SVA infection.
塞尼卡病毒 A（SVA）是一种新兴病毒，会导致鼻子和蹄部起疱，降低猪的生产性能。RSAD2 是一种激进的 S-腺苷甲硫氨酸（SAM）酶，由于其广泛的抗病毒活性，其表达可以抑制各种病毒。然而，SVA 和 RSAD2 之间的调控关系以及作用机制尚不清楚。在这里，我们证明 SVA 感染会增加 RSAD2 mRNA 水平，而 RSAD2 表达则负调控病毒复制，这表现在病毒 VP1 蛋白表达、病毒滴度和感染细胞数量的降低。筛选与 RSAD2 相互作用的病毒蛋白，发现 2C 蛋白与 RSAD2 的相互作用强于其他蛋白。此外，RSAD2 的氨基酸（aa）43-70 对于与 2C 蛋白相互作用至关重要，并且在其抗 SVA 活性中发挥重要作用。RSAD2 是由 I 型干扰素（IFN-I）通过 Janus 激酶信号转导和转录激活因子（JAK-STAT）诱导的，具有抗病毒活性。JAK-STAT 途径抑制剂鲁索替尼和 JAK1 表达的敲低显著降低了 RSAD2 表达水平和抗病毒活性。总之，这些结果表明 RSAD2 通过与病毒 2C 蛋白相互作用来阻断 SVA 感染，并为预防和控制 SVA 感染提供了一种策略。
