Cheng Zhikui, Zhi Xiaoguang, Sun Ge, Guo Wei, Huang Yayun, Sun Weihua, Tian Xiaohui, Zhao Fei, Hu Kanghong
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Sino-Germany Biomedical Center, Hubei University of Technology, Wuhan, 430068, China.
J Med Virol. 2016 Apr;88(4):653-63. doi: 10.1002/jmv.24366. Epub 2015 Oct 16.
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 (Na2SeO3 ) 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 Na2SeO3 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 Na2SeO3 . Below this concentration, Na2SeO3 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 Na2 SeO3 concentration or treatment time. Moreover, the inhibitory effect of Na2SeO3 on HBV replication can be further enhanced by combined treatment with lamivudine, entecavir, or adefovir. Thus, the present study clearly proves that Na2SeO3 suppresses HBV protein expression, transcription, and genome replication in hepatoma cell models in a dose- and time-dependent manner.
乙型肝炎病毒(HBV)感染是全球最严重且普遍的健康问题之一。目前的抗HBV药物存在诸多缺点,如不良反应和耐药性;因此,需要新型潜在的抗HBV试剂。已表明硒(Se)与人免疫缺陷病毒和丙型肝炎病毒感染均有关,但它在HBV感染中的作用仍不清楚。为解决这一问题,将亚硒酸钠(Na2SeO3)应用于三种HBV细胞模型:HepG2.2.15细胞,以及转染了1.1或1.3×HBV质粒的HuH-7细胞。通过细胞计数试剂盒-8检测Na2SeO3的细胞毒性。分别通过酶联免疫吸附测定、Northern印迹和Southern印迹测量病毒抗原表达水平、转录本和衣壳化病毒DNA的水平。在Na2SeO3浓度<2.5μM时,HepG2.2.15细胞或HuH-7细胞中均未观察到明显的细胞毒性。在此浓度以下,Na2SeO3在所有三种测试模型中均抑制HBsAg和HBeAg的产生、HBV转录水平以及基因组DNA的量,且抑制水平随Na2SeO3浓度或处理时间的增加而增强。此外,与拉米夫定、恩替卡韦或阿德福韦联合治疗可进一步增强Na2SeO3对HBV复制的抑制作用。因此,本研究明确证明,Na2SeO3在肝癌细胞模型中以剂量和时间依赖性方式抑制HBV蛋白表达、转录和基因组复制。