Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elu...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297262&type=printable |
| _version_ | 1827046536279752704 |
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| author | Dimitrios G Anastasakis Daniel Benhalevy Nicolas Çuburu Nihal Altan-Bonnet Markus Hafner |
| author_facet | Dimitrios G Anastasakis Daniel Benhalevy Nicolas Çuburu Nihal Altan-Bonnet Markus Hafner |
| author_sort | Dimitrios G Anastasakis |
| collection | DOAJ |
| description | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases. |
| first_indexed | 2024-03-08T05:31:13Z |
| format | Article |
| id | doaj.art-a1cbe667de2442479febe318661cba5f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-02-18T14:38:59Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a1cbe667de2442479febe318661cba5f2024-10-26T05:30:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029726210.1371/journal.pone.0297262Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1.Dimitrios G AnastasakisDaniel BenhalevyNicolas ÇuburuNihal Altan-BonnetMarkus HafnerThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297262&type=printable |
| spellingShingle | Dimitrios G Anastasakis Daniel Benhalevy Nicolas Çuburu Nihal Altan-Bonnet Markus Hafner Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1. PLoS ONE |
| title | Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1. |
| title_full | Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1. |
| title_fullStr | Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1. |
| title_full_unstemmed | Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1. |
| title_short | Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1. |
| title_sort | epigenetic repression of antiviral genes by sars cov 2 nsp1 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297262&type=printable |
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