PABPC4 Inhibits SADS-CoV Replication by Degrading the Nucleocapsid Protein Through Selective Autophagy

Simple SummarySADS-CoV is a newly emerging coronavirus affecting the swine industry worldwide. However, our understanding of its pathogenic pathways remains limited. In this study, the researchers aimed to determine the role of the host factor, poly(A)-binding protein 4 (PABPC4), in SADS-CoV infection. This study found that PABPC4 inhibits SADS-CoV replication by degrading the nucleocapsid protein through selective autophagy. This discovery could potentially contribute to developing novel antiviral strategies to prevent and control SADS-CoV infections, protecting the pig industry from significant economic losses.Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel enteric coronavirus that causes severe clinical diarrhea and intestinal pathological injury in pigs. Selective autophagy is an important mechanism of host defense against virus invasion. However, the mechanism through which SADS-CoV-mediated selective autophagy mediates the innate immune response remains unknown. Here, we report that the host protein PABPC4 can inhibit SADS-CoV replication through targeting and degrading its N protein. Furthermore, we demonstrate that PABPC4 recruits MARCHF8 (an E3 ubiquitin ligase), which ubiquitinates the N protein and is degraded via NDP52/CALCOCO2 (a selective autophagy cargo receptor). Taken together, these findings reveal a new mechanism by which PABPC4 inhibits virus replication, and reveal a new target for antiviral drug development.