Efficient virus assembly, but not infectivity, determines the magnitude of hepatitis C virus-induced interferon alpha responses of plasmacytoid dendritic cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/346456
Title:
Efficient virus assembly, but not infectivity, determines the magnitude of hepatitis C virus-induced interferon alpha responses of plasmacytoid dendritic cells.
Authors:
Grabski, Elena; Wappler, Ilka; Pfaender, Stephanie; Steinmann, Eike ( 0000-0002-8771-4262 ) ; Haid, Sibylle; Dzionek, Andrzej; Pietschmann, Thomas ( 0000-0001-5138-6239 ) ; Kalinke, Ulrich ( 0000-0003-0503-9564 )
Abstract:
Worldwide, approximately 160 million people are chronically infected with hepatitis C virus (HCV), seven distinct genotypes of which are discriminated. The hallmarks of HCV are its genetic variability and the divergent courses of hepatitis C progression in patients. We assessed whether intragenotypic HCV variations would differentially trigger host innate immunity. To this end, we stimulated human primary plasmacytoid dendritic cells (pDC) with crude preparations of different cell culture-derived genotype 2a HCV variants. Parental Japanese fulminant hepatitis C virus (JFH1) did not induce interferon alpha (IFN-α), whereas the intragenotypic chimera Jc1 triggered massive IFN-α responses. Purified Jc1 retained full infectivity but no longer induced IFN-α. Coculture of pDC with HCV-infected hepatoma cells retrieved the capacity to induce IFN-α, whereas Jc1-infected cells triggered stronger responses than JFH1-infected cells. Since the infectivity of virus particles did not seem to affect pDC activation, we next tested Jc1 mutants that were arrested at different stages of particle assembly. These experiments revealed that efficient assembly and core protein envelopment were critically needed to trigger IFN-α. Of note, sequences within domain 2 of the core that vitally affect virus assembly also crucially influenced the IFN-α responses of pDC. These data showed that viral determinants shaped host innate IFN-α responses to HCV.
Affiliation:
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Citation:
Efficient virus assembly, but not infectivity, determines the magnitude of hepatitis C virus-induced interferon alpha responses of plasmacytoid dendritic cells. 2015, 89 (6):3200-8 J. Virol.
Journal:
Journal of virology
Issue Date:
15-Mar-2015
URI:
http://hdl.handle.net/10033/346456
DOI:
10.1128/JVI.03229-14
PubMed ID:
25552725
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorGrabski, Elenaen
dc.contributor.authorWappler, Ilkaen
dc.contributor.authorPfaender, Stephanieen
dc.contributor.authorSteinmann, Eikeen
dc.contributor.authorHaid, Sibylleen
dc.contributor.authorDzionek, Andrzejen
dc.contributor.authorPietschmann, Thomasen
dc.contributor.authorKalinke, Ulrichen
dc.date.accessioned2015-03-10T10:37:45Zen
dc.date.available2015-03-10T10:37:45Zen
dc.date.issued2015-03-15en
dc.identifier.citationEfficient virus assembly, but not infectivity, determines the magnitude of hepatitis C virus-induced interferon alpha responses of plasmacytoid dendritic cells. 2015, 89 (6):3200-8 J. Virol.en
dc.identifier.issn1098-5514en
dc.identifier.pmid25552725en
dc.identifier.doi10.1128/JVI.03229-14en
dc.identifier.urihttp://hdl.handle.net/10033/346456en
dc.description.abstractWorldwide, approximately 160 million people are chronically infected with hepatitis C virus (HCV), seven distinct genotypes of which are discriminated. The hallmarks of HCV are its genetic variability and the divergent courses of hepatitis C progression in patients. We assessed whether intragenotypic HCV variations would differentially trigger host innate immunity. To this end, we stimulated human primary plasmacytoid dendritic cells (pDC) with crude preparations of different cell culture-derived genotype 2a HCV variants. Parental Japanese fulminant hepatitis C virus (JFH1) did not induce interferon alpha (IFN-α), whereas the intragenotypic chimera Jc1 triggered massive IFN-α responses. Purified Jc1 retained full infectivity but no longer induced IFN-α. Coculture of pDC with HCV-infected hepatoma cells retrieved the capacity to induce IFN-α, whereas Jc1-infected cells triggered stronger responses than JFH1-infected cells. Since the infectivity of virus particles did not seem to affect pDC activation, we next tested Jc1 mutants that were arrested at different stages of particle assembly. These experiments revealed that efficient assembly and core protein envelopment were critically needed to trigger IFN-α. Of note, sequences within domain 2 of the core that vitally affect virus assembly also crucially influenced the IFN-α responses of pDC. These data showed that viral determinants shaped host innate IFN-α responses to HCV.en
dc.language.isoenen
dc.titleEfficient virus assembly, but not infectivity, determines the magnitude of hepatitis C virus-induced interferon alpha responses of plasmacytoid dendritic cells.en
dc.typeArticleen
dc.contributor.departmentInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.en
dc.identifier.journalJournal of virologyen

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