数字农科院2.0

Tight junction protein claudin-1 is a novel internalization factor for swine enteric coronaviruses infection

文献类型： 外文期刊

作者： Li, Zhongyuan;Chen, Jianfei;Chen, Yunyan;Hu, Shouping;Li, Huan;Li, Liang;Xue, Mei;Feng, Li

作者机构：

关键词： coronavirus;claudin-1;internalization;spike protein

期刊名称： MBIO

ISSN：

年卷期： 2026 年

页码：

收录情况： SCIE（2025版）

摘要： Swine enteric coronaviruses (SeCoVs), including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine deltacoronavirus (PDCoV), have been reported to use aminopeptidase N (APN) as a cellular receptor. However, APN alone cannot effectively explain the infection of both APN-positive and APN-negative enterocytes by PEDV and TGEV, nor the wide host range of PDCoV, suggesting the involvement of other host factors. In this study, we demonstrate that TGEV infection in piglets upregulates claudin-1 expression not only in infected cells but also in uninfected cells. Claudin-1 levels correlated strongly with TGEV N protein levels in the jejunum of infected piglets. Functional studies revealed that claudin-1 overexpression enhanced cellular susceptibility to TGEV, PEDV, and PDCoV, whereas its knockout significantly attenuated infection. Mechanistically, claudin-1 specifically interacts with the S1 or receptor-binding domain (RBD) of SeCoVs and promotes viral internalization. Furthermore, induction of claudin-1 in piglets promotes PDCoV infection in the intestine. Notably, claudin-1 also binds to the S1 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Collectively, our results identify claudin-1 as a novel internalization factor for porcine enteric coronaviruses, playing a critical role in facilitating infection within the digestive tract, and highlight its potential as a target for future clinical interventions.IMPORTANCEWe observed a downregulation in the expression of the majority of tight junction proteins in intestinal tissues infected with transmissible gastroenteritis virus (TGEV). However, unexpectedly, claudin-1 exhibited a significant upregulation in intestinal epithelial cells. This intriguing finding prompted us to delve deeper into the potential role of claudin-1 in facilitating virus invasion of epithelial cells. Utilizing overexpression and knockout cell lines, we demonstrate that claudin-1 is an internalization factor for swine enteric coronaviruses (SeCoVs), including TGEV, porcine epidemic diarrhea virus (PEDV), and porcine deltacoronavirus (PDCoV). Notably, claudin-1 interacts with the S1 protein of TGEV, PEDV, PDCoV, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spanning across alpha, beta, and delta coronaviruses. Our findings provide deeper insights into the infection mechanisms and pathogenesis of SeCoVs and SARS-CoV-2.

分类号：

  • 相关文献

[1]紧密连接蛋白occludin和claudin-1在猪体内不同组织的分布研究. 骆晓蕾,王玉娥. 2015

[2]紧密连接蛋白occludin和claudin-1在猪机体不同组织的分布研究. 骆晓蕾,郭龙军,谷伟红,冯力,王玉娥. 2016

[3]柔嫩艾美耳球虫感染对雏鸡肠道紧密连接相关蛋白表达的影响. 张艳冰,许笑,古少鹏,蔡建平. 2020

[4]The interactions of flaviviruses with cellular receptors: Implications for virus entry. Muhammad Naveed Anwar,Raheela Akhtar,Muhammad Abid,Shahzad Akbar Khan,Zaib Ur Rehman,Muhammad Tayyub,Muhammad Irfan Malik,Muhammad Khurram Shahzad,Hadia Mubeen,Muhammad Shahzad Qadir,Muddassar Hameed,Abdul Wahaab,Zongjie Li,Ke Liu,Beibei Li,Yafeng Qiu,Zhiyong Ma,Jianchao Wei. 2022

[5]Transferrin Receptor Protein 1 Cooperates with mGluR2 To Mediate the Internalization of Rabies Virus and SARS-CoV-2. Xinxin Wang,Zhiyuan Wen,Huizhen Cao,Jie Luo,Lei Shuai,Chong Wang,Jinying Ge,Xijun Wang,Zhigao Bu,Jinliang Wang. 2023

[6]ADP-ribosylation factor 6 promotes infectious bursal disease virus replication by affecting the internalization process via clathrin. Zhang X.,Gao P.,Wang L.,Liu L.,Wang Q.,Xu Z.,Zhang Y.,Yu Y.,Ma J.. 2024

[7]The TGEV Membrane Protein Interacts with HSC70 To Direct Virus Internalization through Clathrin-Mediated Endocytosis. Zhaoyang Ji,Dong, Hui,Jiao, Ruixue,Zhu, Xiaoyuan,Shi, Hongyan,Chen, Jianfei,Shi, Da,Liu, Jianbo,Jing, Zhaoyang,Zhang, Jialin,Wang, Xiaobo,Ye, Dandan,Zhang, Jiyu,Zhang, Xin,Feng, Li. 2023

[8]Bibliometric analysis and systematic review of the adherence, uptake, translocation, and reduction of micro/nanoplastics in terrestrial plants. Li, Yang,Zhao, Lin,An, Yi,Qin, Li,Qiao, Zhi,Chen, Daying,Li, Yihan,Geng, Hongzhi,Yang, Yongkui. 2024

[9]Salmonella YrbD protein mediates invasion into the host by interacting with β2 integrin. Cao, Jun,Wang, Jinliang,Dang, Guanghui,Ding, Shihao,Lu, Yao,Xu, Qiu,Liu, Siguo,Yu, Shenye. 2025

[10]CD44 mediates the internalization of foot-and-mouth disease virus through macropinocytosis. Wang, Xuefei,Dong, Hu,Wu, Jin'en,Zhang, Yun,Sun, Shiqi,Guo, Huichen. 2025

[11]SPIKE PROTEIN REGION (aa 636-789) OF PORCINE EPIDEMIC DIARRHEA VIRUS IS ESSENTIAL FOR INDUCTION OF NEUTRALIZING ANTIBODIES. Sun, D. B.,Feng, L.,Shi, H. Y.,Chen, J. F.,Liu, S. W.,Chen, H. Y.,Wang, Y. F..

[12]A spike-specific whole-porcine antibody isolated from a porcine B cell that neutralizes both genogroup 1 and 2 PEDV strains. Fu, Fang,Li, Lin,Shan, Lingling,Yang, Beibei,Shi, Hongyan,Zhang, Jiaoer,Feng, Li,Liu, Pinghuang,Wang, Hongfeng.

[13]Screening and identification of B cell antigenic Epitopes of porcine epidemic diarrhea virus spike glycoprotein by phage display. Sun Dong-Bo,Lang Hong-Wu,Shi Hong-Yan,Chen Jian-Fei,Cui Xiao-Chen,Wang Cheng-Bao,Tong You-En,Feng Li. 2007

[14]Expression and antigenic epitopes mapping of receptor binding domain on the spike protein of severe acute respiratory syndrome coronavirus. Rua, RH,Tong, GZ,Wang, YF,Zhou, YJ. 2005

[15]Generating Vesicular Stomatitis Virus Pseudotype Bearing the Severe Acute Respiratory Syndrome Coronavirus Spike Envelope Glycoprotein for Rapid and Safe Neutralization Test or Cell-Entry Assay. Ge, Jinying,Wen, Zhiyun,Wang, Xiyun,Hu, Sen,Liu, Yonggang,Kong, Xiangang,Chen, Hualan,Bu, Zhigao.

[16]Identification of two antigenic epitopes on SARS-CoV spike protein. Hua, RH,Zhou, YJ,Wang, YF,Hua, YZ,Tong, GZ. 2004

[17]A Novel Conserved Linear Neutralizing Epitope on the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein. Rong Hong Hua,Shu Jian Zhang,Bei Niu,Jin Ying Ge,Ting Lan,Zhi Gao Bu. 2023

[18]A New Neutralization Epitope in the Spike Protein of Porcine Epidemic Diarrhea Virus. Liu, Jianbo,Shi, Hongyan,Chen, Jianfei,Zhang, Xin,Shi, Da,Ji, Zhaoyang,Jing, Zhaoyang,Feng, Li. 2022

[19]Recombinant human adenovirus type 5 based vaccine candidates against GIIa- and GIIb-genotype porcine epidemic diarrhea virus induce robust humoral and cellular response in mice. Xin Miao,Liping Zhang,Peng Zhou,Zhongwang Zhang,Ruiming Yu,Xiaoqing Liu,Jianliang Lv,Yonglu Wang,Huichen Guo,Li Pan,Xinsheng Liu. 2023

[20]The N-glycosylation at positions 652 and 661 of viral spike protein negatively modulates porcine deltacoronavirus entry. Hai Ming Wang,Yang Yang Qiao,Yong Gang Liu,Bing Yan Cai,Yue Lin Yang,Hui Lu,Yan Dong Tang. 2024

作者其他论文 更多>>