Rapamycin Enhances HBV Production by Inducing Cellular Autophagy

BACKGROUND: Some reports revealed that rapamycin could reactivate HBV infection. However, the mechanism has not been clearly explained. OBJECTIVES: In this report, we studied the mechanism by which rapamycin enhances HBV replication and expression by inducing cellular autophagy. MATERIALS AND METHODS: HepG2.2.15 cells were treated with rapamycin to induce autophagy. Autophagosomes were observed by fluorescence microscopy and transmission electron microscopy. Autophagy marker protein LC3-Ⅱ/LC3-Ⅰwas detected by Western blotting. HBV DNA and mRNA were determined by real time PCR and Southern blotting. HBsAg was evaluated by ELISA. RESULTS: In HepG2.2.15 cells, HBV DNA and HBsAg increased when host cells were treated with rapamycin and the effect was reversed by autophagy inhibitor, 3-methyladenine (3-MA). CONCLUSIONS: These results indicated a potential explanation for reactivation of HBV infection when patients with hepatitis receive rapamycin.