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...

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Published inPloS one Vol. 19; no. 1; p. e0297262
Main Authors Anastasakis, Dimitrios G, Benhalevy, Daniel, Çuburu, Nicolas, Altan-Bonnet, Nihal, Hafner, Markus
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 26.01.2024
Public Library of Science (PLoS)
Subjects
Analysis
Antiviral Agents - pharmacology
Antiviral drugs
Cell culture
Coronaviruses
COVID-19
COVID-19 - genetics
Cytomegalovirus
Epigenetic inheritance
Epigenetic Repression
Epigenetics
Ethanol
Footprinting
Gene expression
Gene silencing
Genes
Genetic aspects
Genetic transcription
Histones
Humans
Immune evasion
Immunomodulation
Infections
Kinases
Lysine
Messenger RNA
Methylation
Methyltransferase
Molecular dynamics
Plasmids
Proteins
Ribonucleic acid
RNA
SARS-CoV-2 - genetics
SARS-CoV-2 - metabolism
Scientific equipment and supplies industry
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Shutdowns
Transferases
Viral diseases
Viral Nonstructural Proteins - metabolism
Viral proteins
Virus diseases
Viruses
United States
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Summary: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.
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ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0297262