title: CpG oligodeoxynucleotide inhibits HBV replication in a hydrodynamic injection murine model.
abstract: BACKGROUND
  Chronic HBV infection is a significant public health problem and one major cause of liver cirrhosis and hepatocellular carcinoma (HCC). HBV impairs the host immune system and results in immunotolerance, which is a major obstacle to HBV therapy. CpG oligodeoxynucleotide (ODN) is a strong immunostimulant which activates the innate immune response rapidly and has been shown to be an efficient therapy agent in viral infection treatment. Here, we report the anti-HBV activity of CpG-1826 in a hydrodynamic injection murine model.
  
  
  METHODS
  CpG-1826 was administrated intraperitoneally every other day in HBV carrier mice established by tail vein hydrodynamic injection of HBV plasmids. The serum concentrations of HBV surface antigen (HBsAg), HBV e antigen (HBeAg), HBV surface antibody (HBsAb), HBV core antibody (HBcAb), interferon-α (IFN-α) and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA). The activities of alanine aminotransferase (ALT) were determined by ALT kit using a Spectramax Plus spectrophotometer. Hepatic HBV DNA was quantified by quantitative real-time PCR. The expression of HBV core antigen (HBcAg) in liver was detected by immunohistochemistry. Drug toxicity of CpG-1826 was evaluated by body weighting and liver histopathology confirmation.
  
  
  RESULTS
  CpG-1826 administration inhibited HBV replication efficiently with significant reduction of serum HBsAg and HBeAg, hepatic HBcAg and HBV DNA levels. The serum levels of IFN-α, IFN-γ and HBsAb increased but the HBcAb level declined in the CpG-1826 group compared to CpG-1982 and PBS control groups. Results of ALT activity indicated no significant difference among CpG-1826 group, CpG-1982 and PBS control groups. Body weighting and histopathology examination showed no obvious toxicity.
  
  
  CONCLUSIONS
  Given the stimulation activity of a host immune system, CpG ODN is a promising strategy for HBV therapy with more relevant research needed.
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Zhang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Mao
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Sheng-Qi
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004279:DNA, Viral; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006509:Hepatitis B / Q000097:blood / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000097:blood / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma