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The lack of effective vaccines or treatments makes elucidating host\u2010pathogen 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\u2010mediated 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\u2010Traf6\u2010Tollip axis as a promising therapeutic direction.<\/jats:p>","DOI":"10.1155\/tbed\/8776901","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:18:53Z","timestamp":1782803933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The PCK2\u2010Traf6\u2010Tollip Axis Restricts PEDV Replication by Orchestrating Selective Autophagic Degradation of the Viral Nucleocapsid 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