Chicken CH25H inhibits ALV-J replication by promoting cellular autophagy.

Chicken CH25H inhibits ALV-J replication by promoting cellular autophagy.
复制标题

鸡CH 25 H通过促进细胞自噬抑制ALV-J复制。

DOI:
10.3389/fimmu.2023.1093289
复制
发表时间:
2023
影响因子:
7.3
通讯作者:
Zhang, Xiquan
Zhang, Xiquan
中科院分区:
医学2区
文献类型:
--
作者:
Xie, Tingting;Feng, Min;Zhang, Xi;Li, Xiaoqi;Mo, Guodong;Shi, Meiqing;Zhang, Xiquan

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相似文献

自噬在宿主抗病毒防御中起着重要作用。J亚群禽白血病病毒(ALV-J)已被证明抑制自噬,同时促进病毒复制。然而,潜在的自噬机制尚不清楚。胆固醇25-羟化酶(CH 25 H)是一个保守的干扰素刺激基因,可将胆固醇转化为可溶性抗病毒因子25-羟基胆固醇(25 HC)。本研究进一步探讨了CH 25 H在鸡胚成纤维细胞系(DF 1)中抗ALV-J的自噬机制。我们的研究结果发现,CH 25 H的过表达和25 HC处理促进了自噬标志物微管相关蛋白1轻链3 II(LC 3 II)和自噬相关基因5(ATG 5)的表达,同时降低了自噬底物p62/SQSTM 1(p62)在ALV-J感染DF-1细胞中的表达。细胞自噬的诱导也降低ALV-J gp 85和p27的水平。另一方面,ALV-J感染抑制自噬标记蛋白LC 3 II表达。这些发现表明,CH 25 H诱导的自噬是一种有助于ALV-J复制抑制的宿主防御机制。特别是,CH 25 H与CHMP 4 B相互作用,通过促进自噬抑制DF-1细胞中的ALV-J感染,揭示了CH 25 H抑制ALV-J感染的新机制。虽然其潜在机制尚未完全了解,但CH 25 H和25 HC是第一个显示通过自噬抑制ALV-J感染的。
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.
DOI: 10.1038/s41579-018-0003-6
发表时间: 2018-06
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发表时间: 2018-05-01
期刊: Science signaling
影响因子: 7.3
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