State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China.
School of Public Health, Wuhan University, Wuhan, People's Republic of China.
Nat Microbiol. 2024 Oct;9(10):2583-2599. doi: 10.1038/s41564-024-01801-y. Epub 2024 Sep 18.
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.
胆酸是微生物代谢产物，可影响肠道和肝炎病毒的感染，但它们在系统性病毒感染中的功能尚不清楚。在这里，我们发现次级胆酸牛磺胆酸（TLCA）水平升高与严重发热伴血小板减少综合征病毒（SFTSV）感染患者的死亡率降低和病毒血症抑制相关，SFTSV 是一种新兴的蜱传出血热病毒。TLCA 在体外抑制 SFTSV 感染中的病毒复制并减轻宿主炎症，并且通过 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。早期感染时血清中铁和铁蛋白水平升高与 SFTSV 感染患者 TLCA 水平降低和致命结局相关，提示存在潜在的生物标志物。此外，用铁死亡抑制剂或 TLCA 治疗可保护小鼠免受致命 SFTSV 感染。我们的研究结果强调了胆酸治疗出血热病毒感染的治疗潜力。
