Fig. 3: Bile acids-TGR5 axis protects from influenza virus infection.

a–d Room temperature-exposed mice given 0.5 mM of CA (a) or DCA (b) were infected intranasally with 1000 pfu of influenza virus. Mortality (a, b; water, n = 16 mice; CA, n = 17 mice; DCA, n = 17 mice) and virus titer in the lung wash (c, d; water, n = 10 to 16 mice; CA, n = 9 to 16 mice; DCA, n = 10 mice) were measured on indicated days after challenge. e, f MDCK cells were infected with influenza virus PR8 (an amantadine-resistant strain) in the presence or absence of indicated amounts of GW 4064, HY-14229, or amantadine. Cell lysates were collected at 24 h p.i. and analyzed by immunoblotting with indicated antibodies (e). Cell-free supernatants were collected at 24 h p.i. and analyzed for virus titer by standard plaque assay using MDCK cells (f; DMSO, n = 6; GW 4064, n = 6; HY-14229, n = 6). g, h Room temperature-exposed mice given 100 μM of HY-14229 were infected intranasally with 1000 pfu of influenza virus. Virus titer in the lung wash (g; water, n = 8 mice; HY-14229, n = 8 mice) and mortality (h; water, n = 68 mice; HY-14229, n = 73 mice) were measured on indicated days after challenge. Each symbols indicate individual values (c, d, f, g). Data are mean ± s.e.m. Data are pooled from two (a–d) or three (h) independent experiments or are representative of two independent experiments (e–g). Statistical significance was analyzed by two-way analysis of variance (ANOVA) (f), two-tailed unpaired Student’s t test (c, d, g), or two-sided log-rank (Mantel-Cox) test (a, b, h). *P < 0.05, **P < 0.01 (c; 2 days p.i., p = 0.014; d; 2 days p.i., p = 0.0052; 3 days p.i., p = 0.0456; g; 2 days p.i., p = 0.00321).