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Open AccessArticle

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

Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, China
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MA 20742, USA
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2019, 11(6), 498;
Received: 3 May 2019 / Revised: 20 May 2019 / Accepted: 21 May 2019 / Published: 30 May 2019
(This article belongs to the Section Antivirals & Vaccines)
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. View Full-Text
Keywords: chicken; ISG; ALV-J; CH25H chicken; ISG; ALV-J; CH25H
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Xie, T.; Feng, M.; Dai, M.; Mo, G.; Ruan, Z.; Wang, G.; Shi, M.; Zhang, X. Cholesterol-25-hydroxylase Is a Chicken ISG That Restricts ALV-J Infection by Producing 25-hydroxycholesterol. Viruses 2019, 11, 498.

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