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

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.

• Authors: Tingting Xie, Min Feng, Manman Dai, Guodong Mo, Zhuohao Ruan, Guiyan Wang, Meiqing Shi, Xiquan Zhang
• Journal: Viruses (Viruses) Vol. 11 Issue 6 (05 30 2019) ISSN: 1999-4915 [Electronic] Switzerland
• PMID: 31151272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Hydroxycholesterols
• Interferon Type I
• Interferon-alpha
• 25-hydroxycholesterol
• Steroid Hydroxylases
• cholesterol 25-hydroxylase

Topics

• Animals
• Antiviral Agents (pharmacology)
• Avian Leukosis (virology)
• Avian Leukosis Virus (physiology)
• Cell Line
• Chickens (genetics, immunology)
• Female
• Fibroblasts (virology)
• Gene Expression
• Hydroxycholesterols (metabolism)
• Interferon Type I (immunology)
• Interferon-alpha (immunology, pharmacology)
• Leukocytes, Mononuclear (drug effects, virology)
• Male
• Phylogeny
• Poultry Diseases (virology)
• Promoter Regions, Genetic
• Steroid Hydroxylases (genetics)
• Virus Replication (drug effects)