Fig. 4: Identification of SIRT6 as a host virus-restricting factor against HBV.

a, b Introduction of Sirt6 suppressed the expression of HBcAg (a) and HBsAg and HBeAg (b) antigens in Huh7.5.1 cells. c, d Knocking-down endogenous Sirt6 promoted the expression of HBcAg (c) and HBsAg and HBeAg (d) antigens in Huh7.5.1 cells. e, f Effect of SIRT6 enzymatic mutants on HBcAg (e) and HBsAg and HBeAg (f) expression in huh7.5.1 cells. g The effect of SIRT6 wild type or enzymatic deficient mutant on HBV genome replication was measured via southern blotting in HepG2 cells. h The chemical formula and a close-up view of MDL-800 in complex with 2′-O-acyl-ADP ribose (2′-O-acyl-ADPR) motif of human SIRT6 (X-ray structure, PDB number 5Y2F). i, j ELISA shows that MDL800 suppressed the expression of HBcAg (i) and HBsAg and HBeAg (j) antigens in dose-dependent manner in Tet-controlled HBV in HepAD38 cells. k MDL-800 treatment significantly suppressed HBV genome replication intermediates in Huh7 cells. RC relaxed circular, DNA DSL double strand linear DNA, SS single strand DNA. For ELISA, for panel b, n = 2; for others, n = 3. *P < 0.05, **P < 0.01, ***P < 0.001.