Cholesterol-25-hydroxylase Is a Chicken ISG That Restricts ALV-J Infection by Producing 25-hydroxycholesterol
文献类型： 外文期刊
作者： Xie, Tingting 1 ; Feng, Min 1 ; Dai, Manman 3 ; Mo, Guodong 1 ; Ruan, Zhuohao 1 ; Wang, Guiyan 1 ; Shi, Meiqing 4 ; Zhang 1 ;
作者机构： 1.South China Agr Univ, Coll Anim Sci, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Guangzhou 510642, Guangdong, Peoples R China
2.Minist Agr, Key Lab Chicken Genet Breeding & Reprod, Guangzhou 510642, Guangdong, Peoples R China
3.South China Agr Univ, Coll Vet Med, Guangzhou 510642, Guangdong, Peoples R China
4.Univ Maryland, Virginia Maryland Reg Coll Vet Med, Div Immunol, College Pk, MD 20742 USA
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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