tetano
Editor, Senior Moderator
PLoS One
. 2024 Jan 26;19(1):e0297262.
doi: 10.1371/journal.pone.0297262. eCollection 2024. Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1
Dimitrios G Anastasakis[SUP] 1 [/SUP], Daniel Benhalevy[SUP] 1 [/SUP], Nicolas Çuburu[SUP] 2 [/SUP], Nihal Altan-Bonnet[SUP] 3 [/SUP], Markus Hafner[SUP] 1 [/SUP]
Affiliations
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.
. 2024 Jan 26;19(1):e0297262.
doi: 10.1371/journal.pone.0297262. eCollection 2024. Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1
Dimitrios G Anastasakis[SUP] 1 [/SUP], Daniel Benhalevy[SUP] 1 [/SUP], Nicolas Çuburu[SUP] 2 [/SUP], Nihal Altan-Bonnet[SUP] 3 [/SUP], Markus Hafner[SUP] 1 [/SUP]
Affiliations
- PMID: 38277395
- PMCID: PMC10817131
- DOI: 10.1371/journal.pone.0297262
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.