Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

PloS one - 19(2024), 1 vom: 01., Seite e0297262

Sprache:

Englisch

Beteiligte Personen:

Anastasakis, Dimitrios G [VerfasserIn]
Benhalevy, Daniel [VerfasserIn]
Çuburu, Nicolas [VerfasserIn]
Altan-Bonnet, Nihal [VerfasserIn]
Hafner, Markus [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
NSP1 protein, SARS-CoV-2
Viral Nonstructural Proteins

Anmerkungen:

Date Completed 04.02.2024

Date Revised 04.02.2024

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pone.0297262

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367678055