2. Academic Validation
  3. Taurolithocholic acid protects against viral haemorrhagic fever via inhibition of ferroptosis

Taurolithocholic acid protects against viral haemorrhagic fever via inhibition of ferroptosis

  • Nat Microbiol. 2024 Oct;9(10):2583-2599. doi: 10.1038/s41564-024-01801-y.
Xiaojie Zheng # 1,  Yunfa Zhang # 1,  Lingyu Zhang # 1,  Tong Yang 1,  Faxue Zhang 2,  Xi Wang 1 3,  Shu Jeffrey Zhu 4,  Ning Cui 5,  Hongdi Lv 5,  Xiaoai Zhang 1,  Hao Li 6 7 8,  Wei Liu 9 10 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China.
  • 2 School of Public Health, Wuhan University, Wuhan, People's Republic of China.
  • 3 Graduate School of Anhui Medical University, Hefei, People's Republic of China.
  • 4 Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China.
  • 5 The 154th Hospital, Xinyang, People's Republic of China.
  • 6 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China. lihao_1986@126.com.
  • 7 School of Public Health, Wuhan University, Wuhan, People's Republic of China. lihao_1986@126.com.
  • 8 Graduate School of Anhui Medical University, Hefei, People's Republic of China. lihao_1986@126.com.
  • 9 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China. liuwei@bmi.ac.cn.
  • 10 School of Public Health, Wuhan University, Wuhan, People's Republic of China. liuwei@bmi.ac.cn.
  • 11 Graduate School of Anhui Medical University, Hefei, People's Republic of China. liuwei@bmi.ac.cn.
  • # Contributed equally.
PMID: 39294459 DOI: 10.1038/s41564-024-01801-y
Abstract

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.

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