Investigation into the Pancreatic Pathogenesis of SFTSV across Multiple Levels

Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) infection induces hepatitis, myocarditis, and even multi-organ dysfunction with a high mortality rate, while the impact on the pancreas remains unknown. 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 ≥3 × upper limit of normal (ULN)) and 25.8% (elevated serum lipase ≥3 × 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-C motif chemokine receptor 2 (CCR2) and lipoprotein receptor-related 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-inflammatory cytokine upregulation. Pathological analysis of infected murine pancreatic tissues showed acinar cell vacuolization, viral inclusions, and immune cell infiltration. Comparative studies with caerulein-induced pancreatitis models identified C3-mediated 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.