title: IFN-CSP inhibiting hepatitis B virus in HepG2.2.15 cells involves JAK-STAT signal pathway.
abstract: Frequent and high-dose administration of interferon to patients with viral hepatitis results in various side effects. In our previous study, a novel liver-targeting interferon (IFN-CSP) combining Plasmodium region I peptide with IFNα2b was successfully designed and expressed in the Escherichia coli expression systems. This targeting would target the IFNα2b specifically to the liver, thus reducing the adverse events. In the present study, we further investigated the anti-HBV effects and molecular mechanisms of recombinant IFN-CSP in HepG2.2.15 cell line. Hepatitis B surface antigen (HBsAg) and HBe antigen (HBeAg) in the culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA). HBV-DNA was measured by real-time quantitative PCR. HBV core protein was assayed by immunofluorescent and western blot analysis. The expressions of signal transducers and transactivator 1 (STAT1), STAT2, IFN regulatory factor 9 (IRF-9), and 2'-5'-oligoadenylate synthetase 1 (OAS1) were investigated by the reverse transcription PCR and western blot analysis. Results indicate IFN-CSP efficiently inhibited HBsAg and HBeAg secretion, HBV-DNA replication, and HBV core protein expression in HepG2.2.15 cells. The anti-HBV mechanisms involve activation of JAK-STAT signaling and increase of the anti-HBV protein OAS expression. IFN-CSP could be a good substitute for IFNα2b for anti-HBV treatment.
authors: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China ; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China.
authors: Xuemei
authors: 0000-0002-0571-1472
authors: X
authors: Lu
authors: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China ; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China.
authors: Jie
authors: 0000-0002-9555-5476
authors: J
authors: Wang
authors: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China ; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China.
authors: Xiaobao
authors: 0000-0001-5450-1730
authors: X
authors: Jin
authors: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China ; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China.
authors: Yanting
authors: 0000-0001-9149-2415
authors: Y
authors: Huang
authors: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China ; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China.
authors: Wenting
authors: W
authors: Zeng
authors: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China ; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou Higher Education Mega Center, 280 Wai Huan Dong Road, Guangzhou 510006, China.
authors: Jiayong
authors: J
authors: Zhu
mesh_terms: D056945:Hep G2 Cells; D006509:Hepatitis B / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism*; D010961:Plasmodium; D015800:Protozoan Proteins / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D006514:Hepatitis B Surface Antigens; C554158:IFNA2 protein, human; D016898:Interferon-alpha; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; C041595:circumsporozoite protein, Protozoan; D053612:Janus Kinases