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Chicken CH25H inhibits ALV-J replication by promoting cellular autophagy

文献类型: 外文期刊

作者: Xie, Tingting 1 ; Feng, Min 1 ; Zhang, Xi 1 ; Li, Xiaoqi 1 ; Mo, Guodong 1 ; Shi, Meiqing 4 ; Zhang, Xiquan 1 ;

作者机构: 1.South China Agr Univ, Coll Anim Sci, Guangdong Prov Key Lab Agroanim Genom & Mol Breedi, Guangzhou, Peoples R China

2.Minist Agr, Key Lab Chicken Genet Breeding & Reprod, Guangzhou, Guangdong, Peoples R China

3.South China Agr Univ, State Key Lab Conservat & Utilizat Subtrop Agrobio, Guangzhou, Guangdong, Peoples R China

4.Univ Maryland, Virginia Maryland Reg Coll Vet Med, Div Immunol, College Pk, MD USA

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

期刊名称:FRONTIERS IN IMMUNOLOGY ( 影响因子:7.3; 五年影响因子:8.0 )

ISSN: 1664-3224

年卷期: 2023 年 14 卷

页码:

收录情况: SCI

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.

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