Establishment of an ex vivo vascular tissue model to investigate bunyavirus-triggered vascular endothelial injury

ABSTRACT Severe fever with thrombocytopenia syndrome, an emerging infectious disease caused by the tick-borne bunyavirus severe fever with thrombocytopenia syndrome virus (SFTSV), is associated with a high clinical fatality rate of 12%–50%. Vascular endothelial injury triggered by SFTSV infection has been linked to severe disease progression and mortality. Currently, a suitable model to investigate the underlying mechanisms of SFTSV-induced vascular damage is lacking. Here, we show that the ex vivo human vascular tissue can be used as a model for studying bunyavirus-triggered endothelial injury. Both SFTSV and Rift Valley fever virus (RVFV) can successfully infect ex vivo human vascular tissue, as evidenced by detection of viral nucleoprotein and viral amplification in the tissue. Histopathological analysis, TUNEL staining, and endothelial injury-associated transcriptional changes revealed irregular venous tissue structure, luminal endothelial disruption, and apoptosis following infection. This model enables evaluation of antiviral compound efficacy, demonstrating that niclosamide or 4′-fluorouridine significantly inhibits SFTSV and RVFV replication in ex vivo vascular tissues. These findings establish the ex vivo human vascular tissue as a valuable tool for investigating bunyavirus-induced vascular pathogenesis and for evaluating antiviral therapeutics. IMPORTANCE Severe fever with thrombocytopenia syndrome virus and other pathogenic bunyaviruses cause severe human diseases that are frequently associated with vascular dysfunction. However, the mechanisms underlying virus-induced vascular injury remain poorly defined due to the lack of physiologically relevant human tissue models. Here, we establish an ex vivo human vascular tissue model that supports productive bunyavirus infection and enables quantitative assessment of endothelial injury, tissue damage, and antiviral efficacy. Using this model, we demonstrate that bunyavirus infection triggers endothelial disruption and that antiviral compounds can suppress viral replication and alleviate infection-associated tissue injury. This model provides a valuable experimental system for studying virus-vascular interactions and can support antiviral development against emerging bunyaviruses.