Abstract: Objective To investigate the role of small ubiquitin-related modifier (SUMO) specific protease 3 (SENP3) in hepatitis B virus (HBV) infection.Methods To explore the mechanism of SENP3, HepG2.2.15 cell and HBV transgenic mouse were applied for experiments in vivo and vitro using western blot, real-time polymerase chain reaction and immunohistochemistry. Results The HBV DNA of patients was negatively correlated with the content of SENP3 in peripheral blood mononuclear cells. The average protein concentration of SENP3 in healthy control group was 7.4 times higher than that in patient group (P<0.05). In the liver of HBV transgenic mice, the expression of SENP3 was significantly decreased and phosphorylation of protein kinase B (Akt) was 4.1 times higher than that of control group (P<0.01). In HepG2.2.15 cells transfected with HBV DNA whole-genome plasmid, the expression of SENP3 was significantly lower, while the phosphorylation of Akt was 5.2 times higher than that in HepG2 cells (P<0.01). Overexpression of SENP3 in HepG2.215 cells resulted in decreases of Akt phosphorylation and HBV DNA content. Moreover, SENP3 plasmid concentration was negatively correlated with HBV DNA content. When transfecting HepG2.2.15 cells with 100 ng and 500 ng SENP3 plasmids, the concentrations of HBV DNA were reduced from 7.983.03×10⁶ IU/ml to 3.45×10⁶ IU/ml and 1.92×10⁶ IU/ml, respectively. While silencing SENP3 in HepG2.2.15 cells, phosphorylation of Akt was increased 5.6 times (P<0.01).Conclusion The expression of HBV DNA is negatively correlated with the expression of SENP3, which can reduce the level of HBV DNA by inhibiting the phosphorylation of Akt in hepatocytes.

Key words: Small ubiquitin-related modifier specific protease 3, Hepatitis B virus deoxyribonucleic acid, Protein kinase B, Phospho-protein kinase B