Abstract

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.

Highlights

  • The avian leukosis virus subgroup J (ALV-J) is a member of the a-retrovirus genus of retroviridae, causing tumor disease, immunosuppression, and other secondary diseases in chicken

  • Chicken peripheral blood mononuclear cell (PBMC) were treated by ALV-J and IFN-α for 6 h, respectively

  • Compared to untreated PBMC, differentially expressed genes (DEGs) were identified from ALV-J-infected group and IFN-α-treated group by RNA-Seq

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Summary

Introduction

The avian leukosis virus subgroup J (ALV-J) is a member of the a-retrovirus genus of retroviridae, causing tumor disease, immunosuppression, and other secondary diseases in chicken. ALV-J has caused enormous losses to the world poultry industry at the end of the last century [1]. The western world has been successful in the eradication of ALV-J from the breeding flocks. The ALV purification of chicken flocks is a big project that requires a lot of Viruses 2019, 11, 498; doi:10.3390/v11060498 www.mdpi.com/journal/viruses. In developing countries like China, where farms lack management experience and sufficient funds, coupled with the existence of numerous local chicken breeds, ALV purification is a challenge. It is important to change the individual’s resistance to ALV-J from the nature of the genetics, it is difficult. The screening and identification of anti-ALV-J genes is an important strategy in the genetic improvement of chickens. To our knowledge, the systematic identification of anti-ALV-J genes has not been reported

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