Bile acids are microbial metabolites that can impact infection of enteric and hepatitis viruses, but their functions during systemic viral infection remain unclear. Here we show that elevated levels of the secondary bile acid taurolithocholic acid (TLCA) are associated with reduced fatality rates and suppressed viraemia in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne haemorrhagic fever virus. TLCA inhibits viral replication and mitigates host inflammation during SFTSV infection in vitro, and indirectly suppresses SFTSV-mediated induction of ferroptosis by upregulating fatty acid desaturase 2 via the TGR5–PI3K/AKT–SREBP2 axis. High iron and ferritin serum levels during early infection were correlated with decreased TLCA levels and fatal outcomes in SFTSV-infected patients, indicating potential biomarkers. Furthermore, treatment with either ferroptosis inhibitors or TLCA protected mice from lethal SFTSV infection. Our findings highlight the therapeutic potential of bile acids to treat haemorrhagic fever viral infection.

胆汁酸是可影响肠道和肝炎病毒感染的微生物代谢产物，但它们在全身性病毒感染期间的功能仍不清楚。在这里，我们表明，次级胆汁酸牛磺酰胆酸 （TLCA） 水平升高与感染血小板减少综合征病毒 （SFTSV） 的严重发热患者的死亡率降低和病毒血症抑制有关，SFTSV 是一种新兴的蜱传出血热病毒。TLCA 在体外抑制病毒复制并减轻 SFTSV 感染期间的宿主炎症，并通过 TGR5-PI3K/AKT-SREBP2 轴上调脂肪酸去饱和酶 2 间接抑制 SFTSV 介导的铁死亡诱导。感染早期血清铁和铁蛋白水平高与 SFTSV 感染患者的 TLCA 水平降低和致命结果相关，表明潜在的生物标志物。此外，用铁死亡抑制剂或 TLCA 治疗可保护小鼠免受致命的 SFTSV 感染。我们的研究结果强调了胆汁酸治疗出血热病毒感染的治疗潜力。