title: Inhibition of hepatitis C virus RNA replication  by ISG15 does not require its conjugation  to protein substrates by the HERC5 E3 ligase.
abstract: Chronic infection of the liver by hepatitis C virus (HCV) induces a range of host factors including IFN-stimulated genes such as ISG15. ISG15 functions as an antiviral factor that limits virus replication. Previous studies have suggested that ISG15 could influence HCV replication in both a positive and a negative manner. In this report, we determined the effect of ISG15 on HCV RNA replication in two independent cell lines that support viral genome synthesis by inhibiting ISG15 expression through small interfering RNA, short-hairpin RNA and CRISPR/Cas9 gene knockout approaches. Our results demonstrated that ISG15 impairs HCV RNA replication in both the presence and absence of IFN stimulation, consistent with an antiviral role for ISG15 during HCV infection. ISG15 conjugation to protein substrates typically requires the E3 ligase, HERC5. Our results showed that the inhibitory effect of ISG15 on HCV RNA replication does not require its conjugation to substrates by HERC5.
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Domingues
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Connor G G
authors.initials: CGG
authors.lastname: Bamford
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Boutell
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: John
authors.initials: J
authors.lastname: McLauchlan
mesh_terms: D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D016207:Cytokines; C402395:HERC5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D012367:RNA, Viral; D014452:Ubiquitins; C074034:ISG15 protein, human; D044767:Ubiquitin-Protein Ligases