Cholesterol-25-hydroxylase Is a Chicken ISG That Restricts ALV-J Infection by Producing 25-hydroxycholesterol

文献类型： 外文期刊

第一作者： Xie, Tingting

作者： Xie, Tingting;Feng, Min;Mo, Guodong;Ruan, Zhuohao;Wang, Guiyan;Zhang, Xiquan;Xie, Tingting;Mo, Guodong;Ruan, Zhuohao;Wang, Guiyan;Zhang, Xiquan;Dai, Manman;Shi, Meiqing

作者机构：

关键词： chicken; ISG; ALV-J; CH25H

期刊名称：VIRUSES-BASEL （ 影响因子：5.048； 五年影响因子：5.127 ）

ISSN： 1999-4915

年卷期： 2019 年 11 卷 6 期

页码：

收录情况： SCI

摘要： 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-alpha (IFN-alpha) 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-alpha 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.

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