Betaine Inhibits Hepatitis B Virus with an Advantage of Decreasing Resistance to Lamivudine and Interferon α

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• 作者：Mengmeng Zhang ; Xiaoying Wu ; Furao Lai ; Xiaoyuan Zhang ; Hui Wu ; Tian Min
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2016
• 出版时间：May 25, 2016
• 年：2016
• 卷：64
• 期：20
• 页码：4068-4077
• 全文大小：558K
• 年卷期：0
• ISSN：1520-5118

文摘

Betaine (BET) is a native compound known for its ability to protect the liver from toxicants. However, few studies have examined the effects of BET on the most common cause of liver disease, hepatitis B virus (HBV). In this study, the anti-HBV activity of BET was assessed in vitro and in vivo using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and Southern blotting. The resistance of HBV to lamivudine and interferon α is challenging in the clinical treatment of HBV. The effect of BET on resistance was also investigated. The results showed that the secretion of HBsAg (HBV surface antigen), HbeAg (HBV e antigen), and HBV DNA in HepG2.2.15 cells was significantly decreased by BET via suppression of GRP78 expression. In duck HBV (DHBV)-infected ducklings, 1.0 or 2.0 g/kg BET significantly reduced serum DHBV DNA, and DHBV DNA did not rebound after the 5 day withdrawal period. BET suppressed HBV DNA rebound produced by the resistance of HBV to lamivudine and decreased the resistance mutation (rtM204V/I) of HBV DNA. Supplementation of BET may improve the anti-HBV effect of interferon α by increasing the expression of antiviral dsRNA-dependent protein kinase induced by the JAK–STAT (JAK = Janus kinase; STAT = signal transducer and activator of transcription) signaling pathway. These results may provide useful information for the clinical application of BET and solution of HBV drug resistance in anti-HBV therapy.