title: Betaine Inhibits Hepatitis B Virus with an Advantage of Decreasing Resistance to Lamivudine and Interferon α.
abstract: 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.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology , Guangzhou, Guangdong 510006, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wu
authors.forename: Furao
authors.initials: F
authors.lastname: Lai
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Tian
authors.initials: T
authors.lastname: Min
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001622:Betaine / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D000091342:Endoplasmic Reticulum Chaperone BiP; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D019259:Lamivudine / Q000494:pharmacology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D016898:Interferon-alpha; D014764:Viral Proteins; D019259:Lamivudine; D001622:Betaine
keywords: betaine; drug resistance; hepatitis B virus; interferon α; lamivudine