{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:56:46Z","timestamp":1773723406296,"version":"3.50.1"},"reference-count":23,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32330098"],"award-info":[{"award-number":["32330098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Projects of Xizang Autonomous Region","award":["XZ202501ZY0143"],"award-info":[{"award-number":["XZ202501ZY0143"]}]},{"name":"Changsha Science and Technology Plan Natural Science Foundation","award":["kq2402188"],"award-info":[{"award-number":["kq2402188"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["SWU-KT22013"],"award-info":[{"award-number":["SWU-KT22013"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>The Swine hepatitis E virus (SHEV) ORF3 protein is pivotal in pathogenesis, yet its regulation of host metabolic homeostasis via endogenous RNA networks remains unclear. This study aimed to elucidate how the SHEV ORF3-mediated circRNA-miRNA network modulates riboflavin metabolism and triggers the aberrant activation of the ko05212 pathway, while also evaluating their physical interactions using AlphaFold 3 structural simulations. To achieve this, high-throughput RNA sequencing, KEGG pathway analysis, and AlphaFold 3 structural simulations were employed to elucidate the circRNA-miRNA-mRNA regulatory network and potential physical interactions. Transcriptomics revealed a \u201cdual activation\u201d of Riboflavin metabolism and Pancreatic cancer pathways. Specifically, we identified an \u201cENPP Isozyme Switch,\u201d where upregulated hsa_circ_0077855 sponges miR-181a-2-3p, relieving repression of the metabolic enzyme ENPP3 and proto-oncogene KRAS. Furthermore, AlphaFold 3 simulations yielded an extremely low interface predicted Template Modeling score (ipTM = 0.08), refuting direct physical binding, and ORF3 was found to suppress the m6A eraser FTO, suggesting host epigenetic instability. Consequently, SHEV ORF3 induces metabolic remodeling through a dual \u201cepigenetic-post-transcriptional\u201d mechanism: disrupting m6A homeostasis via FTO suppression and constructing a pathogenic ceRNA network via the ENPP3\/miR-181a\/KRAS axis. These findings highlight the critical role of non-coding RNAs in driving the virus-induced \u201cpre-pathological state\u201d.<\/jats:p>","DOI":"10.3390\/vetsci13030253","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Transcriptomics Reveals a SHEV ORF3-Mediated circRNA Network That Disrupts Riboflavin Metabolism and Activates the ko05212 Pathway"],"prefix":"10.3390","volume":"13","author":[{"given":"Weihao","family":"Luo","sequence":"first","affiliation":[{"name":"The College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiya","family":"Li","sequence":"additional","affiliation":[{"name":"The College of Veterinary Medicine, Southwest University, Chongqing 402460, China"},{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengping","family":"Wu","sequence":"additional","affiliation":[{"name":"The College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingjie","family":"Wang","sequence":"additional","affiliation":[{"name":"The College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulong","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leli","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanwei","family":"Jiao","sequence":"additional","affiliation":[{"name":"The College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nrgastro.2017.150","article-title":"Hepatitis E virus: Advances and challenges","volume":"15","author":"Nimgaonkar","year":"2018","journal-title":"Nat. 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