scholarly journals CD81/CD9 tetraspanins aid plasmacytoid dendritic cells in recognition of hepatitis C virus-infected cells and induction of interferon-alpha

Hepatology ◽  
2013 ◽  
Vol 58 (3) ◽  
pp. 940-949 ◽  
Author(s):  
Shuye Zhang ◽  
Karen Kodys ◽  
Gregory J. Babcock ◽  
Gyongyi Szabo
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Plasmacytoid Dendritic Cells ◽  
Infected Cells

scholarly journals Efficient Virus Assembly, but Not Infectivity, Determines the Magnitude of Hepatitis C Virus-Induced Interferon Alpha Responses of Plasmacytoid Dendritic Cells

2014 ◽  
Vol 89 (6) ◽  
pp. 3200-3208 ◽  
Author(s):  
Elena Grabski ◽  
Ilka Wappler ◽  
Stephanie Pfaender ◽  
Eike Steinmann ◽  
Sibylle Haid ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Virus Assembly ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Infected Cells ◽  
Interferon Responses

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.IMPORTANCEAlthough pegylated IFN-α plus ribavirin currently is the standard of care for the treatment of chronic hepatitis C virus infection, not much is known about the relevance of early interferon responses in the pathogenesis of hepatitis C virus infection. Here, we addressed whether intragenotypic variations of hepatitis C virus would account for differential induction of type I interferon responses mounted by primary blood-derived plasmacytoid dendritic cells. Surprisingly, a chimeric genotype 2a virus carrying the nonstructural genes of Japanese fulminant hepatitis C virus (JFH1) induced massive type I interferon responses, whereas the original genotype 2a JFH1 strain did not. Our detailed analyses revealed that, not the virus infectivity, but rather, the efficiency of virus assembly and core protein envelopment critically determined the magnitude of interferon responses. To our knowledge, this is the first example of hepatitis C virus-associated genetic variations that determine the magnitude of innate host responses.

scholarly journals Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection

2010 ◽  
Vol 107 (16) ◽  
pp. 7431-7436 ◽  
Author(s):  
K. Takahashi ◽  
S. Asabe ◽  
S. Wieland ◽  
U. Garaigorta ◽  
P. Gastaminza ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Plasmacytoid Dendritic Cells ◽  
Infected Cells

scholarly journals Hepatitis C Virus Is a Weak Inducer of Interferon Alpha in Plasmacytoid Dendritic Cells in Comparison with Influenza and Human Herpesvirus Type-1

PLoS ONE ◽  
2009 ◽  
Vol 4 (2) ◽  
pp. e4319 ◽  
Author(s):  
Françoise Gondois-Rey ◽  
Clélia Dental ◽  
Philippe Halfon ◽  
Thomas F. Baumert ◽  
Daniel Olive ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Human Herpesvirus ◽  
Plasmacytoid Dendritic Cells ◽  
Herpesvirus Type ◽  
Human Herpesvirus Type

scholarly journals Hepatitis C Virus Fails To Activate NF- B Signaling in Plasmacytoid Dendritic Cells

2011 ◽  
Vol 86 (2) ◽  
pp. 1090-1096 ◽  
Author(s):  
C. Dental ◽  
J. Florentin ◽  
B. Aouar ◽  
F. Gondois-Rey ◽  
D. Durantel ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Plasmacytoid Dendritic Cells

scholarly journals TLR Ligand-Dependent Activation of Naive CD4 T Cells by Plasmacytoid Dendritic Cells Is Impaired in Hepatitis C Virus Infection

2007 ◽  
Vol 178 (7) ◽  
pp. 4436-4444 ◽  
Author(s):  
Nicole L. Yonkers ◽  
Benigno Rodriguez ◽  
Kimberly A. Milkovich ◽  
Robert Asaad ◽  
Michael M. Lederman ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Cd4 T Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Hepatitis C Virus Infection
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