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Open AccessArticle

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

1
Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
2
Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, China
3
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
4
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; https://doi.org/10.3390/v11060498
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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