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-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.
Highlights
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family members consist of a series of cytidine deaminases, including APOBEC1, -2, -3A, -3B, -3C, -3E, -3F, -3G and activation-induced cytidine deaminase (AID)
(A) reverse transcriptase-polymerase chain reaction (RT-PCR) electrophotogram of APOBEC3G mRNA after HepG2.2.15 cells were treated with various concentrations and times of IFN- ; (B) Detection of APOBEC3G mRNA by real-time fluorescent quantitative RT-PCR after HepG2.2.15 cells were treated with various concentrations of IFN- (0 U/mL, 1 U/mL, U/mL, U/mL, U/mL, U/mL)
RT-PCR after HepG2.2.15 cells were treated with IFN- of 103 U/mL for 2, 4, 6, 8, 10, 12 hours; (D) Detection of APOBEC3G protein by Western-blot after HepG2.2.15 cells were treated with various concentrations of IFN- for 8 hours
Summary
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family members consist of a series of cytidine deaminases, including APOBEC1, -2, -3A, -3B, -3C, -3E, -3F, -3G and activation-induced cytidine deaminase (AID). APOBEC3G, a protein member of the APOBEC superfamily, has been suggested to play an important role in innate anti-viral immunity. APOBEC3G is expressed markedly in liver [1]. APOBEC3G can induce nucleoside mutations from deoxycytidine to deoxyuridine in the viral genome [2]. APOBEC3G has been identified as an intrinsic factor able to restrict replication of human immunodeficiency virus type 1 (HIV-1) lacking the viral accessory protein. Vif [3,4]. It has been revealed that APOBEC3G inhibits hepatitis B virus (HBV)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
