2. Academic Validation
  3. ALG6 orchestrates coronavirus replication via the endoplasmic reticulum stress-autophagy axis

ALG6 orchestrates coronavirus replication via the endoplasmic reticulum stress-autophagy axis

  • Cell Rep. 2026 Mar 17;45(4):117108. doi: 10.1016/j.celrep.2026.117108.
Yanan Fu 1,  Meijie Gao 1,  Zhen Fu 1,  Limeng Sun 1,  Zhelin Su 1,  Yubei Tan 1,  Yixin Xiang 1,  Yuejun Shi 1,  Shengsong Xie 2,  Guiqing Peng 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
  • 2 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. Electronic address: [email protected].
  • 3 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Key Laboratory of Prevention & Control for African Swine Fever and Other Major Pig Diseases, Ministry of Agriculture and Rural Affairs, Wuhan, China; Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, P.R. China. Electronic address: [email protected].
PMID: 41855202 DOI: 10.1016/j.celrep.2026.117108
Abstract

Coronaviruses (CoVs) constitute a major global health threat, and their replication is inseparable from host factors. Investigating host-virus interactions is critical for elucidating the CoV life cycle. Here, we identify alpha-1,3-glucosyltransferase (ALG6) as an essential host factor for CoV replication. Mechanistically, its catalytic activity governs transmissible gastroenteritis virus (TGEV) replication, and ALG6 knockout (KO) inhibits viral entry by downregulating the receptor Aminopeptidase N (ANPEP). Moreover, our results indicate that ALG6 KO triggers endoplasmic reticulum (ER) stress, resulting in suppressed viral replication. Further investigations demonstrate that ALG6 KO predominantly hinders viral replication by triggering downstream Autophagy induced by ER stress. Transmission electron microscopy analysis reveals that ALG6 KO disrupts the formation of double-membrane vesicles (DMVs) during the initial stages of viral replication. In summary, our findings underscore the crucial role of ALG6 in the replication of CoVs, presenting a promising avenue for the development of potential therapeutic strategies against future CoV infections.

Keywords

ALG6; CP: microbiology; ER stress; autophagy; coronavirus; replication.

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