SADS-CoV nucleocapsid protein antagonizes DAD1-mediated STING activation to prevent cytosolic DNA sensing.
TL;DR
It is revealed that the SADS-CoV N protein evades host innate immunity by disrupting DAD1-mediated activation, pointing to potential targets for antiviral strategies.
Abstract
The STING pathway is pivotal in defense against RNA viruses; however, its involvement in swine acute diarrhea syndrome coronavirus (SADS-CoV) infection remains unclear. This study reveals a dual mechanism where in SADS-CoV triggers STING activation via nuclear envelope rupture but subsequently evades immunity through its nucleocapsid (N) protein. Mechanistically, this process involves chromatin leakage that activates the cGAS-STING pathway, triggering interferon responses. The endoplasmic reticulum-resident protein defender against cell death 1 (DAD1) plays a key role in promoting STING phosphorylation and trafficking to the Golgi apparatus. The SADS-CoV N protein binds to STING to block its activation and translocation, disrupting DAD1-mediated antiviral signaling. Notably, the E368A mutation in the N protein weakens STING binding and impairs immune suppression. These findings reveal that the SADS-CoV N protein evades host innate immunity by disrupting DAD1-mediated activation, pointing to potential targets for antiviral strategies.