Cholesterol-25-hydroxylase Is a Chicken ISG That Restricts ALV-J Infection by Producing 25-hydroxycholesterol
Cholesterol-25-hydroxylase Is a Chicken ISG That Restricts ALV-J Infection by Producing 25-hydroxycholesterol
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胆固醇 25 羟化酶是一种鸡 ISG，通过产生 25 羟基胆固醇来限制 ALV-J 感染
DOI：
10.3390/v11060498
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发表时间：
2019
期刊：
影响因子：
4.7
通讯作者：
Zhang Xiquan
中科院分区：
文献类型：
--
作者：
Xie Tingting;Feng Min;Dai Manman;Mo Guodong;Ruan Zhuohao;Wang Guiyan;Shi Meiqing;Zhang Xiquan
J亚群禽白血病病毒（ALV-J）是一种鸡逆转录病毒，给养禽业造成巨大的经济损失。干扰素刺激基因（ISG）对于控制病毒感染至关重要。本研究采用RNA-Seq技术，在鸡外周血单个核细胞（PBMC）中鉴定了897个IFN-α诱导的I型ISGs。此外，我们进一步鉴定了152个潜在的抗ALV-J鸡I型ISG。在这些潜在的抗ALV-J ISG中，选择鸡胆固醇25-羟化酶（chCH 25 H）用于在鸡胚成纤维细胞系（DF 1）中的进一步抗病毒机制研究。chCH 25 H基因位于6号染色体上，在系统发育树中与哺乳动物CH 25 H聚在一个不同的组中。chCH 25 H的核心启动子区位于−75/−1序列内。结果表明，鸡IFN-α和ALV-J均可诱导DF 1细胞产生chCH 25 H。在感染后48 h（hpi），chCH 25 H的过表达显著抑制ALV-J在DF 1细胞中的复制。此外，ALV-J复制在chCH 25 H敲除的DF 1细胞中显著增强。此外，我们证明了chCH 25 H通过产生25-羟基胆固醇（25 HC）而不是I型和II型干扰素来限制ALV-J感染。本研究共鉴定出152个抗鸡I型ALV-J的ISG，表明chCH 25 H的产物25 HC可作为天然抗病毒药物用于控制ALV-J感染。
The avian leukosis virus subgroup J (ALV-J) belongs to the chicken retrovirus that causes enormous economic losses in the poultry industry. Interferon-stimulated genes (ISGs) are critical for controlling virus infections. Here, we identified 897 type I ISGs induced by interferon-α (IFN-α) in chicken peripheral blood mononuclear cell (PBMC) by RNA-Seq. In addition, we further identified 152 potential anti-ALV-J chicken type I ISGs. Among these potential anti-ALV-J ISGs, chicken cholesterol 25-hydroxylase (chCH25H) was selected for further antiviral mechanism studies in chicken embryo fibroblast cell lines (DF1). The gene chCH25H is located on chromosome 6 and clustered in a distinct group with mammals CH25H in the phylogenetic tree. The core promoter region of chCH25H was located within −75/−1 sequence. We found that chCH25H was induced by chicken IFN-α and ALV-J in DF1 cells. The overexpression of chCH25H significantly inhibited ALV-J replication in DF1 cells at 48 h post infection (hpi). In addition, ALV-J replication was significantly enhanced in the chCH25H- knockout DF1 cells. Furthermore, we demonstrated that chCH25H restricted ALV-J infection through the production of 25-hydroxycholesterol (25HC), rather than type I and II interferon. Our results identified 152 potential anti-ALV-J chicken type I ISGs and revealed that 25HC, the product of chCH25H, could be used as a natural antiviral agent to control ALV-J infection.