{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:30:28Z","timestamp":1789659028277,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014599","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the General Program of National Natural Science Foundation of China","award":["32372962"],"award-info":[{"award-number":["32372962"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Major Scientific and Technological Projects in Agricultural Biological Breeding","award":["2023ZD040430403"],"award-info":[{"award-number":["2023ZD040430403"]}]},{"DOI":"10.13039\/501100013141","name":"Jilin Provincial Key Research and Development Plan Project","doi-asserted-by":"publisher","award":["20250102273JC"],"award-info":[{"award-number":["20250102273JC"]}],"id":[{"id":"10.13039\/501100013141","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the National Key Research and Development Program of China","award":["2025YFF1000800"],"award-info":[{"award-number":["2025YFF1000800"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Porcine epidemic diarrhea virus (PEDV) represents a severe threat to the global swine industry. Its infection process involves intricate virus\u2013host interactions and immune evasion mechanisms, but effective therapeutic targets remain elusive. In this study, we identified protein arginine methyltransferase 3 (PRMT3) as a novel regulatory factor that significantly modulates PEDV infection via genome-wide CRISPR\/Cas9 knockout library screening. Knockout or inhibition of PRMT3 markedly enhanced PEDV infection in multiple cell lines, including LLC-PK1, IPEC-J2, and primary porcine intestinal epithelial cells. Mechanistic investigations revealed that PRMT3 can restrict PEDV infection by interacting with vesicle-associated membrane protein-associated protein A (VAPA). Further analysis revealed that VAPA facilitates cholesterol transport through binding to oxysterol-binding protein (OSBP) and inhibits the autophagic degradation of the viral nucleocapsid (N) protein, with both processes being critical for promoting PEDV infection in host cells. A detailed analysis revealed that K52 within its major sperm protein (MSP) domain interacts with D404 and D405 in the two phenylalanines in an acidic tract (FFAT)-like motifs of the N protein, and these interactions proved essential for PEDV infection. In summary, this is the first study to identify and validate the PRMT3\u2013VAPA\u2013N protein autophagic degradation axis as a key pathway through which PRMT3 suppresses PEDV infection, with VAPA acting as an essential host factor for PEDV pathogenesis. These findings uncover novel signaling pathways and molecular targets for the development of anti-PEDV therapeutics.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014599","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:57:03Z","timestamp":1788890223000},"page":"e1014599","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["PRMT3 restricts porcine epidemic diarrhea virus replication by disrupting the interaction between VAPA and the viral nucleocapsid protein"],"prefix":"10.1371","volume":"22","author":[{"given":"He-Yong","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Animal Genome Editing Technology Innovation Center, College of Animal Sciences, Jilin University","place":["Changchun, Jilin, 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