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Interferon-alpha Induces High Expression of APOBEC3G and STAT-1 in Vitro and in Vivo
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China
* Author to whom correspondence should be addressed.
Received: 23 August 2010; in revised form: 13 September 2010 / Accepted: 14 September 2010 / Published: 20 September 2010
Abstract: 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-a, 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-a. It is found that IFN-a 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-a are significantly higher than that of the patients with non-response to IFN-a treatment. It is suggested that inducing intracellular APOBEC3G expression may be one of anti-HBV mechanisms of IFN-a, and IFN-a-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-a treatment.
Keywords: STAT-1; interferon-alpha; APOBEC3G; HepG2.2.15 cell; chronic hepatitis B
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MDPI and ACS Style
Chen, H.; Wang, L.-W.; Huang, Y.-Q.; Gong, Z.-J. Interferon-alpha Induces High Expression of APOBEC3G and STAT-1 in Vitro and in Vivo. Int. J. Mol. Sci. 2010, 11, 3501-3512.
Chen H, Wang L-W, Huang Y-Q, Gong Z-J. Interferon-alpha Induces High Expression of APOBEC3G and STAT-1 in Vitro and in Vivo. International Journal of Molecular Sciences. 2010; 11(9):3501-3512.
Chen, Hui; Wang, Lu-Wen; Huang, Yan-Qing; Gong, Zuo-Jiong. 2010. "Interferon-alpha Induces High Expression of APOBEC3G and STAT-1 in Vitro and in Vivo." Int. J. Mol. Sci. 11, no. 9: 3501-3512.