Interferon-alpha induces high expression of APOBEC3G and STAT-1 in vitro and in vivo.
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.
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China; E-Mails: chenh8253@163.com (H.C.); wangluw8253@163.com (L.W.); huangyq@163.com (Y.H.).
Hui
H
Chen
Lu-Wen
LW
Wang
Yan-Qing
YQ
Huang
Zuo-Jiong
ZJ
Gong
D000071480:APOBEC-3G Deaminase; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase