Liu Chunyun, Kong Ning, Liu Hailong, Zhang Yu, Qin Wenzhen, Zhao Wenli, Yang Xinyu, Wang Yahe, Cao Xinyu, Liu Tian, Liu Yuchang, Sun He, Tong Wu, Yu Hai, Zheng Hao, Lan Daoliang, Xie Shengsong, Tong Guangzhi, Shan Tongling
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, China.
J Virol. 2025 Jan 31;99(1):e0183724. doi: 10.1128/jvi.01837-24. Epub 2024 Dec 13.
Infection with porcine epidemic diarrhea virus (PEDV) results in enormous economic damage to the global swine industry. PEDV starts its life cycle by binding to the receptors of host cells and adsorbing onto the cellular surfaces. However, it is still unknown how PEDV adsorbs onto the surface of host cells and the mechanism beneath the interplay of host cell transmembrane protein with PEDV proteins. FSTL1, which is a secreted glycoprotein, participates in diverse pathological and physiological processes, including immune modulation and cell proliferation and differentiation. The transmembrane protein, TLR4, serves as a pattern recognition receptor recognizing a broad spectrum of pathogens, which exerts a crucial effect on the host immune system. In this study, we identified that FSTL1 promoted PEDV infection. Further studies demonstrated the interactive relationship between FSTL1 and PEDV structural proteins (N and S2). In addition, we also confirmed that TLR4 interacted with FSTL1 and PEDV N, S1, and S2 proteins on the cell surface. Moreover, FSTL1 promoted the interaction of TLR4 and PEDV and induced viral adsorption to host cells. This study offers explicit evidence that FSTL1 and TLR4 act as mediators for host cell adsorption of PEDV by interacting with PEDV N/S proteins.IMPORTANCEAs a highly infectious porcine epidemic diarrhea virus (PEDV)-induced intestinal condition of swine, porcine epidemic diarrhea (PED) results in a 100% death rate among suckling piglets and poses a serious economic burden to global swine farming. Therefore, it is essential to investigate the mechanism of virus infection, replication, and proliferation. Virus begins its life cycle by binding to the receptor of host cells and adsorbing onto the cellular surfaces. However, it remains unclear how PEDV adsorbs onto the host cell surfaces. This study revealed that host protein FSTL1 interacted with the PEDV N and S2 proteins, while TLR4 interacted with the FSTL1 and PEDV proteins (N, S1, and S2). Moreover, we thoroughly and methodically demonstrated that FSTL1 was engaged in the PEDV internalization and attachment processes by promoting the recognition of PEDV N\S proteins by TLR4 and induced the viral adsorption to host cells.
猪流行性腹泻病毒（PEDV）感染给全球养猪业造成了巨大的经济损失。PEDV通过与宿主细胞受体结合并吸附在细胞表面来开始其生命周期。然而，PEDV如何吸附到宿主细胞表面以及宿主细胞跨膜蛋白与PEDV蛋白相互作用的机制仍不清楚。FSTL1是一种分泌型糖蛋白，参与多种病理和生理过程，包括免疫调节以及细胞增殖和分化。跨膜蛋白TLR4作为一种模式识别受体，可识别多种病原体，对宿主免疫系统发挥关键作用。在本研究中，我们发现FSTL1促进了PEDV感染。进一步研究证明了FSTL1与PEDV结构蛋白（N和S2）之间的相互作用关系。此外，我们还证实TLR4在细胞表面与FSTL1以及PEDV的N、S1和S2蛋白相互作用。而且，FSTL1促进了TLR4与PEDV的相互作用，并诱导病毒吸附到宿主细胞上。本研究提供了明确的证据，表明FSTL1和TLR4通过与PEDV的N/S蛋白相互作用，作为宿主细胞吸附PEDV的介质。
重要性
作为一种由高传染性的猪流行性腹泻病毒（PEDV）引起的猪肠道疾病，猪流行性腹泻（PED）导致哺乳仔猪的死亡率达100%，给全球养猪业带来了沉重的经济负担。因此，研究病毒感染、复制和增殖的机制至关重要。病毒通过与宿主细胞受体结合并吸附在细胞表面来开始其生命周期。然而，PEDV如何吸附到宿主细胞表面仍不清楚。本研究表明，宿主蛋白FSTL1与PEDV的N和S2蛋白相互作用，而TLR4与FSTL1以及PEDV蛋白（N、S1和S2）相互作用。此外，我们全面且系统地证明了FSTL1通过促进TLR4对PEDV N\S蛋白的识别参与PEDV的内化和附着过程，并诱导病毒吸附到宿主细胞上。
