17-AAG, an inhibitor of heat shock protein 90, down-regulates hepatitis B virus replication

Objective To investigate the potential involvement of the heat shock protein 90 (HSP90) in transforming growth factor-beta (TGFβ) signaling activation in hepatocytes, and to observe the effect of the HSP90 inhibitor, 17-AAG, on hepatitis B virus (HBV) replication.Methods HepG2 cells were treated with 17-AAG and total RNA was extracted to measure PAI-1 (SERPINE1) expression by real-time RT-PCR.Meanwhile, HepG2 cells were also transfected with the HBV1.3 HBV replicative plasmid after two hours of pretreatment with 17-AAG and TGFβ or SB431542.At day 4 post-transfection, HBV core particles were extracted and HBV replicative intermediates were detected by Southern blotting analysis.HBV surface antigen (HBsAg) was measured by ELISA.Results 17-AAG down-regulated mRNA expression of PAI-1 in HepG2 cells.HBV replication and HBsAg expression were inhibited upon 17-AAG treatment.However, activation of the TGFβ signaling pathway had no effect on HBV replication.Conclusion HSP90 is involved in the TGFβ signaling pathway during HBV infection.The HSP90 inhibitor, 17-AAG, can inhibit HBV replication and HBsAg expression through a TGFβ-independent signaling mechanism.