About: IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection

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About: IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection
Creator	Kim, Sojeong Shin, Eui-Cheol Chung, Jae-Hee Hong, Seon-Hui Kim, Yoon, Seung Park, Su-Hyung Soo, Pil Ho, Min
Source	PMC
abstract	Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-ΔG genotype, which encodes functional IFN-λ4 protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness. HCV infection induced IFN-λ4 expression at mRNA and protein levels in primary human hepatocytes (PHHs). In hepatoma cells, IFNL4 gene transfection or recombinant IFN-λ4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent manner and potently blocked IFN-α signalling. The ISG15/USP18-mediated IFN-α unresponsiveness was demonstrated by transfection of siRNAs targeting ISG15 and/or USP18. This potent IFN-λ4 effect was related to prolonged ISG expression after IFNL4 gene transfection. DAA treatment of HCV-infected PHHs reduced the expression of IFN-λs, including IFN-λ4, and restored IFN-α responsiveness. These results demonstrate that virus-induced IFN-λ4 potently blocks IFN-α signalling by inducing high protein levels of ISG15 and USP18. Moreover, the data clearly demonstrate that DAA therapy restores IFN-α responsiveness in HCV-infected cells.
has issue date	2017-06-19(xsd:dateTime)
bibo:doi	10.1038/s41598-017-04186-7
bibo:pmid	28630501
has license	cc-by
sha1sum (hex)	065a4e7e1e488c1c21dff5602c39e91232a9adbc
schema:url	https://doi.org/10.1038/s41598-017-04186-7
resource representing a document's title	IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection
has PubMed Central identifier	PMC5476576
has PubMed identifier	28630501
schema:publication	Sci Rep
resource representing a document's body	covid:065a4e7e1e488c1c21dff5602c39e91232a9adbc#body_text
is schema:about of	named entity 'functional' named entity 'protein' named entity 'hepatocytes' named entity 'signalling' named entity 'hepatocytes' named entity 'DAA' named entity 'OPEN' named entity 'IFN-α' named entity 'BIOLOGICAL' named entity 'RELATED' named entity 'THESE' named entity 'transfection' named entity 'responsiveness' named entity 'HCV' named entity 'cells' named entity 'IRF9' named entity 'ISG15' named entity 'transfected' named entity 'IFN' named entity 'USP18' named entity 'protein' named entity 'immunoblotting' named entity 'telaprevir' named entity 'demonstrate' named entity 'demonstrated' named entity 'therapy' named entity 'transfection' named entity 'IFN-α' named entity 'study' named entity 'transfection' named entity 'protein' named entity 'IFN' named entity 'mRNA' named entity 'IFN' named entity 'USP18' named entity 'IFN-α' named entity 'infection' named entity 'IFNL4' named entity 'transfection' named entity 'recombinant' named entity 'IFN' named entity 'treatment response' named entity 'protein' named entity 'IFN' named entity 'ISG15' named entity 'IFN' named entity 'IFN' named entity 'virus' named entity 'IFNAR2' named entity 'protein' named entity 'upregulation' named entity 'ISGs' named entity 'ISG15' named entity 'IFNL4' named entity 'protein' named entity 'Transfection' named entity 'IFN' named entity 'HCV' named entity 'immunoblotting' named entity 'recombinant' named entity 'ISG15' named entity 'IFN' named entity 'ISG15' named entity 'recombinant' named entity 'transfected' named entity 'genotype' named entity 'ISG15' named entity 'IFN' named entity 'treatment response' named entity 'ISG15' named entity 'genotype' named entity 'DAAs' named entity 'hepatocytes'

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