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Published on: October 28, 2019
The PCK2-Traf6-Tollip Axis Restricts PEDV Replication by Orchestrating Selective Autophagic Degradation of the Viral
Ao Gao1,2,3, Xinyu Yang2, Wenzhen Qin2
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, China, henau.edu.cn.
Abstract:
Porcine epidemic diarrhea virus (PEDV) is a devastating enteric pathogen in neonatal piglets, causing outbreaks with high mortality. The lack of effective vaccines or treatments makes elucidating host-pathogen interactions essential for developing control strategies. In this study, we identify phosphoenolpyruvate carboxykinase 2 (PCK2) as a host restriction factor that targets the viral nucleocapsid (N) protein for degradation, thereby suppressing PEDV replication. This PCK2-mediated antiviral effect was reversed by autophagy inhibitors, indicating the involvement of a selective autophagic. Mechanistically, we found that PCK2, the N protein, the E3 ubiquitin ligase Traf6, and the cargo receptor Tollip form a functional complex. Depletion of either Traf6 or Tollip disrupted the autophagy pathway, restored N protein stability, and consequently rescued viral replication from PCK2 inhibition. This study unveils a novel antiviral mechanism in which PCK2 orchestrates the selective autophagic degradation of the PEDV N protein, highlighting the PCK2-Traf6-Tollip axis as a promising therapeutic direction.
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