Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro
Marek’s disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene th...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/8/1652 |
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| author | Nitin Kamble Vishwanatha R. A. P. Reddy Ben Jackson Faisal R. Anjum Chidiebere C. Ubachukwu Ajit Patil Shahriar Behboudi |
| author_facet | Nitin Kamble Vishwanatha R. A. P. Reddy Ben Jackson Faisal R. Anjum Chidiebere C. Ubachukwu Ajit Patil Shahriar Behboudi |
| author_sort | Nitin Kamble |
| collection | DOAJ |
| description | Marek’s disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread. |
| first_indexed | 2024-03-10T23:31:10Z |
| format | Article |
| id | doaj.art-e60816498a9f4dc589142f1436aa3d76 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T23:31:10Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e60816498a9f4dc589142f1436aa3d762023-11-19T03:19:45ZengMDPI AGViruses1999-49152023-07-01158165210.3390/v15081652Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In VitroNitin Kamble0Vishwanatha R. A. P. Reddy1Ben Jackson2Faisal R. Anjum3Chidiebere C. Ubachukwu4Ajit Patil5Shahriar Behboudi6Avian Immunology Group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NE, UKAvian Immunology Group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NE, UKAvian Immunology Group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NE, UKAvian Immunology Group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NE, UKAvian Immunology Group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NE, UKAvian Immunology Group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NE, UKAvian Immunology Group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NE, UKMarek’s disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.https://www.mdpi.com/1999-4915/15/8/1652Marek’s disease virusvirus replicationIFN-stimulated genes25-hydroxycholesterol27-hydroxycholesterolCH25H |
| spellingShingle | Nitin Kamble Vishwanatha R. A. P. Reddy Ben Jackson Faisal R. Anjum Chidiebere C. Ubachukwu Ajit Patil Shahriar Behboudi Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro Viruses Marek’s disease virus virus replication IFN-stimulated genes 25-hydroxycholesterol 27-hydroxycholesterol CH25H |
| title | Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro |
| title_full | Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro |
| title_fullStr | Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro |
| title_full_unstemmed | Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro |
| title_short | Inhibition of Marek’s Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro |
| title_sort | inhibition of marek s disease virus replication and spread by 25 hydroxycholesterol and 27 hydroxycholesterol in vitro |
| topic | Marek’s disease virus virus replication IFN-stimulated genes 25-hydroxycholesterol 27-hydroxycholesterol CH25H |
| url | https://www.mdpi.com/1999-4915/15/8/1652 |
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