Interferon-inducible Protein 6-16 (IFI-6-16, ISG16) promotes Hepatitis C virus replication in vitro

Interferon-inducible protein 6-16 (IFI-6-16, ISG16) is one of the interferon stimulated genes (ISGs) whose expression levels can be induced by type I interferons. Previous studies from our group indicated that higher expression levels of ISG16 were detected in the pre-treatment liver tissues of patients chronically infected with hepatitis C virus (HCV) who do not respond to interferon-based therapy. However, its role in HCV production is not well defined. This study is to test the effect of over-expression of ISG16 on HCV RNA replication and IFN anti-HCV activity in both HCV replicon cells and JFH-1 HCV culture system (HCVcc). Expression plasmid of ISG16 was constructed and transfected into HCV replicon cells or JFH-1 HCV culture system. After confirmation of the successful expression of ISG16 at mRNA (real-time PCR) and protein (Western Blot) levels, HCV RNA level was analyzed by real-time quantitative PCR in the absence or presence of interferon-α. Over-expression of ISG16 promoted HCV RNA replication in both the Con1b replicon and the HCV JFH-1-based cell culture system and blunted the anti-HCV activity of IFN-α. In conclusion, Over-expression of ISG16 promotes HCV RNA replication and rescues the IFNα-mediated anti-HCV activity.