Chicken CH25H inhibits ALV-J replication by promoting cellular autophagy

Frontiers in Immunology

Immunology

Meiqing Shi¹  Min Feng²  Tingting Xie³  Xi Zhang³  Guodong Mo³  Xiaoqi Li³  Xiquan Zhang³ 

[1] Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD, United States;Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China;Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China;Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China;State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou, Guangdong, China;

关键词: chicken;    ALV-J;    CH25H;    ISG;    autophagy;   

DOI  :  10.3389/fimmu.2023.1093289

 received in 2022-11-08, accepted in 2023-02-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

Autophagy plays an important role in host antiviral defense. The avian leukosis virus subgroup J (ALV-J) has been shown to inhibit autophagy while promoting viral replication. The underlying autophagic mechanisms, however, are unknown. Cholesterol 25-hydroxylase (CH25H) is a conserved interferon-stimulated gene, which converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol (25HC). In this study, we further investigated the autophagic mechanism of CH25H resistance to ALV-J in chicken embryonic fibroblast cell lines (DF1). Our results found that overexpression of CH25H and treatment with 25HC promoted the autophagic markers microtubule-associated protein 1 light chain 3 II (LC3II) and autophagy-related gene 5(ATG5), while decreased autophagy substrate p62/SQSTM1 (p62) expression in ALV-J infection DF-1 cells. Induction of cellular autophagy also reduces the levels of ALV-J gp85 and p27. ALV-J infection, on the other hand, suppresses autophagic marker protein LC3II expression. These findings suggest that CH25H-induced autophagy is a host defense mechanism that aids in ALV-J replication inhibition. In particular, CH25H interacts with CHMP4B and inhibits ALV-J infection in DF-1 cells by promoting autophagy, revealing a novel mechanism by which CH25H inhibits ALV-J infection. Although the underlying mechanisms are not completely understood, CH25H and 25HC are the first to show inhibiting ALV-J infection via autophagy.

【 授权许可】

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Copyright © 2023 Xie, Feng, Zhang, Li, Mo, Shi and Zhang