FUT8-mediated core fucosylation of receptor APN drives entry of multiple alphacoronaviruses

  • PLoS Pathog. 2026 May 18;22(5):e1014227. doi: 10.1371/journal.ppat.1014227.
Limeng Sun  1  2 ,  Yixin Xiang  1  2 ,  Yichen Yang  1  2 ,  Yubei Tan  1  2 ,  Zhelin Su  1  2 ,  Zhen Fu  1  2 ,  Yanan Fu  1  2 ,  Shengsong Xie  3 ,  Guiqing Peng  1  2  4  5
Affiliations
  • 1. State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  • 2. Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
  • 3. Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, China.
  • 4. Key Laboratory of Prevention & Control for African Swine Fever and Other Major Pig Diseases, Ministry of Agriculture and Rural Affairs, Wuhan, China.
  • 5. Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China.
PMID: 42149951 DOI: 10.1371/journal.ppat.1014227
Abstract

Understanding the interaction mechanisms between coronaviruses (CoVs) and their hosts is crucial for understanding the viral replication cycle and identifying novel Antiviral targets. In this study, we found alpha-(1,6)-fucosyltransferase (FUT8), via its fucosyltransferase activity, is involved in the several alphacoronaviruses (α-CoVs) spike-receptor Aminopeptidase N (APN) interaction to regulate viral entry. Mechanistically, pAPN lacking FUT8-mediated modification showed no binding to the transmissible gastroenteritis virus (TGEV) RBD. The viral entry depends on core fucosylation at pAPN N736. Further pAPN glycoproteomic analysis confirmed that core fucosylation at N736 is indeed present in wild-type (WT) cells but almost abolished in KO cells, highlighting that FUT8 facilitates viral entry by mediating core fucosylation of pAPN N736. Interestingly, FUT8 is also essential for the entry of canine and feline CoVs, which use APN as their receptor, by mediating core fucosylation at N747 and N740 on canine and feline APN, respectively, demonstrating that FUT8 has a conserved function across these species. Overall, this study uncovers the role of FUT8 in multiple α-CoVs entry, revealing the importance of core fucosylation in viral replication and identifying FUT8 as a potential broad-spectrum Antiviral target.

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