title: ISG12a inhibits HCV replication and potentiates the anti-HCV activity of IFN-α through activation of the Jak/STAT signaling pathway independent of autophagy and apoptosis.
abstract: Interferon stimulated (sensitive) genes (ISGs) are the effector molecules downstream of type I/III interferon (IFN) signaling pathways in host innate immunity. ISG12a can be induced by IFN-α. Although ISG12a has been reported to inhibit the replication of HCV, the exact mechanism remains to be determined. In this study, we investigated the possible mechanisms of ISG12a anti- HCV property by exploring the production of type I IFN and the activation of Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway, apoptosis and autophagy in Huh7.5.1 cells transiently transfected with ISG12a over-expression plasmid. Interestingly, we found that ISG12a inhibited HCV replication in both Con1b replicon and the HCV JFH1-based cell culture system and potentiated the anti-HCV activity of IFN-α. ISG12a promoted the production of IFN α/β and activated the type I IFN signaling pathway as shown by increased p-STAT1 level, higher Interferon sensitive response element (ISRE) activity and up-regulated ISG levels. However, ISG12a over-expression did not affect cell autophagy and apoptosis. Data from our current study collectively indicated that ISG12a inhibited HCV replication and potentiated the anti-HCV activity of IFN-α possibly through induced production of type I IFNs and activation of Jak/STAT signaling pathway independent of autophagy and cell apoptosis.
authors: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Provincial Key Laboratory for Transfusion-transmitted Infectious Diseases of Sichuan Province, Chengdu, Sichuan, 610052 China.
authors: Yanzhao
authors: Y
authors: Chen
authors: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Provincial Key Laboratory for Transfusion-transmitted Infectious Diseases of Sichuan Province, Chengdu, Sichuan, 610052 China.
authors: Baihai
authors: B
authors: Jiao
authors: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Provincial Key Laboratory for Transfusion-transmitted Infectious Diseases of Sichuan Province, Chengdu, Sichuan, 610052 China.
authors: Min
authors: M
authors: Yao
authors: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Provincial Key Laboratory for Transfusion-transmitted Infectious Diseases of Sichuan Province, Chengdu, Sichuan, 610052 China.
authors: Xuezhen
authors: X
authors: Shi
authors: Chengdu University, Sichuan Industrial Institute of Antibiotics, Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, China.
authors: Zhebin
authors: Z
authors: Zheng
authors: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Provincial Key Laboratory for Transfusion-transmitted Infectious Diseases of Sichuan Province, Chengdu, Sichuan, 610052 China. Electronic address: shilin-li@hotmail.com.
authors: Shilin
authors: S
authors: Li
authors: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Provincial Key Laboratory for Transfusion-transmitted Infectious Diseases of Sichuan Province, Chengdu, Sichuan, 610052 China; Toronto General Research Institute, University of Toronto, Toronto, ON M5G 1L6 Canada. Electronic address: Limin_chen_99@yahoo.com.
authors: Limin
authors: L
authors: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D015870:Gene Expression; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication
chemical_list: C406887:IFI27 protein, human; D007370:Interferon Type I; D016898:Interferon-alpha; D008565:Membrane Proteins; D050791:STAT Transcription Factors; D016899:Interferon-beta; D053612:Janus Kinases
keywords: Apoptosis; Autophagy; HCV; IFN-α; ISG12a; Jak/STAT