SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35878012.
- Also identified by DOI 10.1073/pnas.2204539119 and PMC identifier 9371684.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the <i>Ifnb1</i> mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-β production, which inhibits SARS-CoV-2 replication. Our findings reveal a target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.
Medical subject headings
- COVID-19
- Carrier Proteins
- Interferon Type I
- Viral Nonstructural Proteins