TGEV NSP1 enhances viral replication through antagonizing stress granule formation

Stress granules (SGs) are membrane-less organelles that form in response to adverse external stimuli. Upon viral invasion, SGs formation can serve as a cellular defence mechanism against infection. Transmissible gastroenteritis virus (TGEV), an α-coronavirus with a large positive-sense single-stranded RNA genome, causes diarrhoea, vomiting, dehydration, and even fatality in piglets. Previous studies have shown that coronaviruses employ various strategies to inhibit the SGs formation, thereby facilitating viral replication. However, the interplay between TGEV infection and the SGs formation remains unclear. In this study, we demonstrate that the SGs formation can enhance antiviral innate immunity mediated through the retinoic acid-inducible gene I (RIG-I) signaling pathway, thereby inhibiting TGEV replication. Nevertheless, TGEV counteracts the SGs formation by reducing the protein level of Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) to promote its own replication. Among the TGEV-encoded proteins, non-structural protein 1 (NSP1) exhibits the strongest inhibitory effect on the SGs formation. In summary, our study systematically elucidated the relationship between TGEV and the SGs formation, providing insights into the mechanism of TGEV pathogenesis and a theoretical foundation for identifying novel anti-coronavirus targets.