Extended Data Fig. 4: TLCA depends on TGR5-PI3K/AKT-SREBP2 axis to block SFTSV replication.
From: Taurolithocholic acid protects against viral haemorrhagic fever via inhibition of ferroptosis
a, Enhancing effect of TGR5 (INT-777) and Akt (sc79) agonists on the expression of SREBP2 and FADS2. Indicated protein in cells post-treated with INT-777 or sc79 at different time were measured. b,c, SFTSV-infected cells were treated with TGR5 (INT-777) and Akt (sc79) agonists at indicated concentrations for 24 h. Intracellular SFTSV RNA levels (b) and supernatant viral titers (c) were measured, respectively; n = 4 biologically independent samples. d, FADS2 knockdown THP-1 cells were infected with SFTSV and treated with INT-777 or sc79 for 24 h. Intracellular SFTSV RNA levels were examined by RT-qPCR; n = 4 biologically independent samples. e,f, SFTSV-infected THP-1 cells were treated with TLCA (200 μM) plus SBI-115 (TGR5 inhibitor; 20 μM) or TLCA plus T-βMCA (FXR inhibitor; 10 μM) for 24 h. Intracellular SFTSV RNA levels (e) and supernatant viral titers (f) were measured, respectively; n = 3 biologically independent samples. Data were presented as mean ± s.d. The two-sided p values were examined using One-way ANOVA followed by Tukey’s multiple comparisons test for comparison of continuous variables among multiple groups (b-d), or Student’s t test for comparison of variables between two groups (e,f). Representative images of three independent replicates were shown in immunoblotting analysis (a).
