Sodium selenite suppresses hepatitis B virus transcription and replication in human hepatoma cell lines

Cheng, Zhikui; Zhi, Xiaoguang; Sun, Ge; Guo, Wei; Huang, Yayun; Sun, Weihua; Tian, Xiaohui; Zhao, Fei; Hu, Kanghong

Hepatitis B virus (HBV) infection is one of the most serious and prevalent health problems worldwide. Current anti‐HBV medications have a number of drawbacks, such as adverse effects and drug resistance; thus, novel potential anti‐HBV reagents are needed. Selenium (Se) has been shown to be involved in both human immunodeficiency virus and hepatitis C virus infections, but its role in HBV infection remains unclear. To address this, sodium selenite (Na(2)SeO(3)) was applied to three HBV cell models: HepG2.2.15 cells, and HuH‐7 cells transfected with either 1.1 or 1.3× HBV plasmids. Cytotoxicity of Na(2)SeO(3) was examined by Cell Counting Kit‐8. Levels of viral antigen expression, transcripts, and encapsidated viral DNA were measured by enzyme‐linked immunosorbent assay, northern blot, and Southern blot, respectively. There was no obvious cytotoxicity in either HepG2.2.15 or HuH‐7 cells with <2.5 µM Na(2)SeO(3). Below this concentration, Na(2)SeO(3) suppressed HBsAg and HBeAg production, HBV transcript level, and amount of genomic DNA in all three tested models, and suppression level was enhanced in line with increases in Na(2)SeO(3) concentration or treatment time. Moreover, the inhibitory effect of Na(2)SeO(3) on HBV replication can be further enhanced by combined treatment with lamivudine, entecavir, or adefovir. Thus, the present study clearly proves that Na(2)SeO(3) suppresses HBV protein expression, transcription, and genome replication in hepatoma cell models in a dose‐ and time‐dependent manner. J. Med. Virol. 88:653–663, 2016. © 2015 Wiley Periodicals, Inc.