Effects of the SIRT3 Activator on HBV Transcription and Replication
XU Hongyan, JIANG Hui, QIN Yiping, REN Fang, REN Jihua*
The aim of this study was to characterize the role of Honokiol, an activator of SIRT3, in HBV transcription and replication. HepG2-NTCP cells and primary human hepatocytes were inoculated with HBV, then the cells were treated with Honokiol at 5 μmol/L, 10 μmol/L and 20 μmol/L concentrations for 10 days. Next, the intracellular HBV DNA, cccDNA and HBV RNAs levels were analyzed by Real-time quantitative PCR. The intracellular HBV DNA was further evaluated by Southern blot. SIRT3-KO cells were constructed, then the effect of Honokiol on HBV DNA, cccDNA and HBV RNAs were determined after SIRT3 knockout. The mouse model of HBV infection were developed by hydrodynamic injection of pCMV-KRAB-Cre and prcccDNA. After a week, the mouse began intraperitoneal injections of Honokiol for 20 days. Serum HBV DNA, liver HBV DNA, liver cccDNA and RNAs were evaluated by Real-time quantitative PCR. The results showed that intracellular HBV DNA and HBV RNAs levels were reduced by Honokiol treatment in a dose-dependent manner. Moreover, Honokiol significantly reduced HBV cccDNA transcriptional activity. Honokiol cannot play a role in anti-HBV after SIRT3 knockout. Furthermore, the serum HBV DNA, liver HBV DNA and HBV RNAs as well as cccDNA transcriptional activity were also decreased on account of the injecting Honokiol in mouse model. These findings indicate that Honokiol can inhibit HBV transcription and replication.
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