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

• Published in: International journal of molecular sciences Vol. 11; no. 9; pp. 3501 - 3512
• Main Authors: Chen, Hui, Wang, Lu-Wen, Huang, Yan-Qing, Gong, Zuo-Jiong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.09.2010; Molecular Diversity Preservation International (MDPI)
• Subjects: Adolescent; Adult; Antiviral Agents - pharmacology; APOBEC-3G Deaminase; APOBEC3G; Apolipoproteins; Case-Control Studies; Cell culture; chronic hepatitis B; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Enzymes; Genomes; Hep G2 Cells; Hepatitis B; Hepatitis B - metabolism; Hepatitis B virus - drug effects; Hepatitis B virus - physiology; Hepatocytes - drug effects; Hepatocytes - metabolism; HepG2.2.15 cell; Humans; Infections; Infectious diseases; Interferon; interferon-alpha; Interferon-alpha - pharmacology; Kinases; Liver; Male; Polypeptides; Proteins; Signal transduction; STAT-1; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; Viral infections; Virus Replication - drug effects; United States > US; China; HepG2.2.15 cell; chronic hepatitis B; STAT-1; interferon-alpha; APOBEC3G
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.