2. Academic Validation
  3. 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

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

  • Virus Res. 2017 Jan 2;227:231-239. doi: 10.1016/j.virusres.2016.10.013.
Yanzhao Chen 1,  Baihai Jiao 1,  Min Yao 1,  Xuezhen Shi 1,  Zhebin Zheng 2,  Shilin Li 3,  Limin Chen 4
Affiliations

Affiliations

  • 1 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.
  • 2 Chengdu University, Sichuan Industrial Institute of Antibiotics, Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, China.
  • 3 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.
  • 4 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.
PMID: 27777077 DOI: 10.1016/j.virusres.2016.10.013
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.

Keywords

Apoptosis; Autophagy; HCV; IFN-α; ISG12a; Jak/STAT.

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