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Hepatitis C virus fails to activate NF-kappaB signaling in plasmacytoid dendritic cells


Plasmacytoid dendritic cells (pDCs) respond to viral infection by production of interferon α (IFN-α), proinflammatory cytokines and cell differentiation. The elimination of hepatitis C virus (HCV) in more than 50% of chronically infected patients by treatment with IFN-α suggests that pDCs can play an important role in the control of HCV infection. pDCs exposed to HCV-infected hepatoma cells, in contrast to cell-free HCV virions, produce large amounts of IFN-α.

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To further investigate the molecular mechanism of HCV sensing, we studied whether exposure of pDCs to HCV-infected hepatoma cells activates in parallel to interferon regulatory factor 7 (IRF7)-mediated production of IFN-α also nuclear factor kappa B (NF-κB)-dependent pDC responses such as expression of the differentiation markers CD40, CCR7, CD86, and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), and secretion of the proinflammatory cytokines TNF-α and interleukin 6 (IL-6).


We demonstrate that exposure of pDCs to HCV-infected hepatoma cells surprisingly did not induce phosphorylation of NF-κB or cell surface expression of CD40, CCR7, CD86, and TRAIL, or secretion of TNF-α and IL-6. In contrast, CpG-A and CpG-B induced production of TNF-α and IL-6 in pDCs exposed to the HCV-infected hepatoma cells, showing that cell-associated virus did not actively inhibit toll-like receptor (TLR)-mediated NF-κB phosphorylation.


Our results suggest that cell associated HCV signals in pDCs via endocytosis-dependent mechanism and IRF7 but not via NF-κB pathway. In spite of IFN-α induction, cell-associated HCV does not induce a full functional response of pDCs. These findings contribute to the understanding of evasion of immune responses by HCV.

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Correspondence to Ruzena Stranska.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Stranska, R., Florentin, J., Dental, C. et al. Hepatitis C virus fails to activate NF-kappaB signaling in plasmacytoid dendritic cells. Retrovirology 9 (Suppl 1), O5 (2012).

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