Apolipoprotein B mRNA-editing enzyme catalytic-polypeptide 3G (APOBEC3G) is a potent inhibitor of infection by a wide range of retroviruses. Although recent reports have suggested that human APOBEC3G exerts antiviral activity against hepatitis B virus, APOBEC3G expression is normally low in the human liver. To clarify the role of APOBEOG in cellular defenses against hepatitis Viruses, the regulation of the APOBEOG expression was investigated in human hepatocytes. Endogenous transcripts of nine APOBEC family members were barely detectable in quiescent liver cells. However, APOBEC3G was significantly up-regulated in response to interferon-alpha (IFN-alpha) stimulation in HepG2 Huh-7, and primary human hepatocytcs. IFN regulatory factor elements that are important for IFN-inducible promoter activity were identified 5' upstream from the human APOBEC3G gene. Our findings provided the first evidence showing that APOBEOG is induced by IFN stimulation in human hepatocytes and thus could be involved in host defense mechanisms directed against hepatitis Viruses. (c) 2006 Elsevier Inc. All rights reserved.