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In a retrospective analysis of clinical parameters in a cohort of 290 patients with severe fever with thrombocytopenia syndrome (SFTS), it is observed that pancreatic injury biomarkers in 19.4% (elevated serum amylase \u22653 \u00d7 upper limit of normal (ULN)) and 25.8% (elevated serum lipase \u22653 \u00d7 ULN). Notably, 17.6% of patients met the diagnostic criteria for clinically confirmed pancreatitis. Mechanistic studies using human pancreatic organoids and murine models demonstrated that SFTSV directly infects pancreatic tissue, facilitated by viral receptors C\u2010C motif chemokine receptor 2 (CCR2)\u00a0and lipoprotein receptor\u2010related protein 1 (LRP1), provoking cell death in pancreatic tissue. Transcriptomic profiling revealed that SFTSV infection triggers a robust innate immune response characterized by interferon pathway activation and pro\u2010inflammatory cytokine upregulation. Pathological analysis of infected murine pancreatic tissues showed acinar cell vacuolization, viral inclusions, and immune cell infiltration. Comparative studies with caerulein\u2010induced pancreatitis models identified C3\u2010mediated complement hyperactivation as a key pathological driver. The studies identified that SFTSV exhibits a specific pancreatic tropism, with direct infection leading to cell death and initiating a strong inflammatory immune response, resulting in viral pancreatitis.<\/jats:p>","DOI":"10.1002\/advs.202515862","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T19:31:35Z","timestamp":1760556695000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Investigation into the Pancreatic Pathogenesis of SFTSV across Multiple Levels"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaohan","family":"Liu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Anhui Medical University Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical School Anhui Medical University Hefei 230032 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