SARS-CoV STRESS GRANULES

Viral genes expression is impeded by activation of cellular stress responses like global inhibition of protein translation and formation of stress granules (SGs). Stress granules are large macromolecular aggregates that contain translation initiation complexes and mRNAs. Their formation lead to translational repression, and stress granules actively signal to maintain translational block, activates innate immunity response, and repress apoptosis. Ras-GTPase-activating protein SH3 domain-binding protein 1/2 (G3BP1, G3BP2) initiate the assembly of SGs by forming homo-multimer and hetero-multimer with each other. La-related protein 4B (LARP4B) is another cytosolic protein that accumulates in stress granules. Under physiological conditions, LARP4B interacts with the cytosolic poly(A) binding protein 1 (PABPC1) and the receptor for activated C Kinase (RACK1), a component of the 40S ribosomal subunit and activates translation. So, its recruitment in SGs and sequestration of a large number of cellular mRNAs directly contribute to the general translation inhibition.