Efficient virus assembly, but not infectivity, determines the magnitude of hepatitis C virus-induced interferon alpha responses of plasmacytoid dendritic cells.
Grabski et al_final.pdf
allowed publisher's PDF
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
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.
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.
AffiliationInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
JournalJournal of virology
The following license files are associated with this item:
- Toll-Like Receptor 7 (TLR-7) and TLR-9 Agonists Improve Hepatitis C Virus Replication and Infectivity Inhibition by Plasmacytoid Dendritic Cells.
- Authors: Dominguez-Molina B, Machmach K, Perales C, Tarancon-Diez L, Gallego I, Sheldon JL, Leal M, Domingo E, Ruiz-Mateos E
- Issue date: 2018 Dec 1
- Hepatitis C Virus Stimulates Murine CD8α-Like Dendritic Cells to Produce Type I Interferon in a TRIF-Dependent Manner.
- Authors: Pfaender S, Grabski E, Detje CN, Riebesehl N, Lienenklaus S, Steinmann E, Kalinke U, Pietschmann T
- Issue date: 2016 Jul
- Hepatitis C virus (HCV) core protein-induced, monocyte-mediated mechanisms of reduced IFN-alpha and plasmacytoid dendritic cell loss in chronic HCV infection.
- Authors: Dolganiuc A, Chang S, Kodys K, Mandrekar P, Bakis G, Cormier M, Szabo G
- Issue date: 2006 Nov 15
- Hepatitis C virus alternate reading frame protein decreases interferon-α secretion in peripheral blood mononuclear cells.
- Authors: Xu X, Yu X, Deng X, Yue M, Zhang J, Zhu D, Zhou Z, Zhai X, Xu K, Zhang Y
- Issue date: 2014 Feb
- Hepatitis C virus fails to activate NF-κB signaling in plasmacytoid dendritic cells.
- Authors: Dental C, Florentin J, Aouar B, Gondois-Rey F, Durantel D, Baumert TF, Nunes JA, Olive D, Hirsch I, Stranska R
- Issue date: 2012 Jan