Interferon-alpha induces high expression of APOBEC3G and STAT-1 in vitro and in vivo

Int J Mol Sci. 2010 Sep 20;11(9):3501-12. doi: 10.3390/ijms11093501.


To investigate whether the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway participates in the regulation of APOBEC3G (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) gene transcription and to study the molecular mechanisms of interferon resistance in patients with chronic hepatitis B (CHB), changes in APOBEC3G and STAT-1 expression levels in HepG2.2.15 cells after treatment with various concentrations of IFN-α, were detected using real-time RT-PCR and Western-blot. In addition, the differences in STAT-1 and APOBEC3G expression in liver tissues were also observed in patients with different anti-viral responses to IFN-α. It is found that IFN-α suppressed HBV replication and expression markedly in HepG2.2.15 cells, and simultaneously enhanced APOBEC3G expression in a dose- or time-dependent manner within a certain range. Moreover, a corresponding gradual increase in STAT-1 expression levels was also observed. The expression levels of STAT-1 and APOBEC3G in the liver of CHB patients with a complete response to IFN-α are significantly higher than that of the patients with non-response to IFN-α treatment. It is suggested that inducing intracellular APOBEC3G expression may be one of anti-HBV mechanisms of IFN-α, and IFN-α-induced APOBEC3G expression may be via the JAK-STAT signaling pathway. Moreover, interferon resistance may be related to the down-regulation of STAT-1 expression in the patients who had non-response to IFN-α treatment.

Keywords: APOBEC3G; HepG2.2.15 cell; STAT-1; chronic hepatitis B; interferon-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase
  • Adolescent
  • Adult
  • Antiviral Agents / pharmacology*
  • Case-Control Studies
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism*
  • Hep G2 Cells
  • Hepatitis B / metabolism*
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / physiology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Interferon-alpha / pharmacology*
  • Male
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • Virus Replication / drug effects


  • Antiviral Agents
  • Interferon-alpha
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase