I collaboration with Nahum Sonenberg's lab at McGill University (Canada) we report the discovery of a novel mechanism by which SARS-CoV2, the virus that causes COVID19 disease, hijacks a cellular mechanism to block production of the key anti-viral cytokine Interferon-ß.
We previously discovered that the mRNA cap-binding protein 4EHP plays a key role in mediating the repression of mRNA translation induced by microRNAs. This mechanism is also important for fine-tuning the expression of production of Interferon-ß in the cell to avoid unintended over-activation of the immune system.
In this new study, we show that the the Non-Structural Protein 2 (NSP2) produced by SARS-CoV-2 binds the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to 4EHP, thereby repressing translation of the Ifnb1 mRNA and leading to inefficient immune response to viral infection. Our findings reveal a new target for rescuing the antiviral innate immune response to SARS-CoV-https://www.biorxiv.org/content/10.1101/2022.01.19.476693v12.