Zhang Qian, Wei Qinglan, Guan Tong, Guo Weiting, Jiang Lixin, Cai Siqi, Zhuang Yunlu, Hu Yujie, Zhang Guihong, Lu Gang, Gong Lang
Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou, China; National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou, China.
Vet Microbiol. 2025 Jul;306:110495. doi: 10.1016/j.vetmic.2025.110495. Epub 2025 May 10.
Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV) has significantly harmed the global pig industry economically. Interferons can induce the expression of interferon-stimulated genes (ISGs) that encode various natural antiviral immune effectors. Notably, swine interferon-induced transmembrane proteins (SwIFITMs) have not been thoroughly investigated in the context of PEDV. In the present research, we explored the anti-PEDV effects of SwIFITMs. Both interferon and PEDV were found to upregulate swine IFITM mRNA levels. Swine IFITM knockdown results showed that SwIFITM1a, -1b, and -2 most significantly reduced PEDV replication. By overexpressing SwIFITMs and establishing a SwIFITM-expressing Vero cell line, we identified SwIFITM2 as having the most pronounced anti-PEDV effect. SwIFITM2 inhibited PEDV entry phase. Additionally, SwIFITM2 interacted with PEDV S2 and N proteins in a dose-dependent manner. Furthermore, it exhibited high co-localization with caveolin-1, while demonstrating the lowest co-localization ratio with clathrin. Upon infection with PEDV, the co-localization of caveolin-1 and PEDV S2 or N protein significantly increased compared with control in the presence of SwIFITM2, indicating that SwIFITM2 may play an antiviral role by confining PEDV within caveolin-1. This study elucidates the anti-PEDV mechanisms of SwIFITMs, providing critical insights into their potential roles in viral pathogenesis and host defense.
由猪流行性腹泻病毒（PEDV）引起的猪流行性腹泻（PED）给全球养猪业造成了巨大的经济损失。干扰素可诱导干扰素刺激基因（ISGs）的表达，这些基因编码各种天然抗病毒免疫效应因子。值得注意的是，猪干扰素诱导跨膜蛋白（SwIFITMs）在PEDV感染的背景下尚未得到充分研究。在本研究中，我们探讨了SwIFITMs对PEDV的抗病毒作用。研究发现，干扰素和PEDV均可上调猪IFITM的mRNA水平。猪IFITM基因敲低结果表明，SwIFITM1a、-1b和-2对PEDV复制的抑制作用最为显著。通过过表达SwIFITMs并建立表达SwIFITM的Vero细胞系，我们确定SwIFITM2具有最显著的抗PEDV作用。SwIFITM2抑制PEDV的进入阶段。此外，SwIFITM2与PEDV的S2和N蛋白以剂量依赖的方式相互作用。此外，它与小窝蛋白-1高度共定位，而与网格蛋白的共定位率最低。在感染PEDV后，与对照组相比，在存在SwIFITM2的情况下，小窝蛋白-1与PEDV S2或N蛋白的共定位显著增加，这表明SwIFITM2可能通过将PEDV限制在小窝蛋白-1中来发挥抗病毒作用。本研究阐明了SwIFITMs的抗PEDV机制，为其在病毒发病机制和宿主防御中的潜在作用提供了重要见解。
