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

作者：Chenchen Zhao, Yan Qin, Haixin Huang, Wei Chen, Yanqing Hu, Xinyu Zhang, Yuying Li, Tian Lan, Wenchao Sun · 发表于：Veterinary Sciences · 年份：2025 · DOI：10.3390/vetsci12030257 · 被引用次数：5 · 研究领域：Autophagy in Disease and Therapy、CRISPR and Genetic Engineering、Endoplasmic Reticulum Stress and Disease

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.