Volume 9 Supplement 1

Abstracts from the 17th International Symposium on HIV and Emerging Infectious Diseases (ISHEID)

Open Access

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

  • Ruzena Stranska1Email author,
  • Jonathan Florentin1,
  • Clélia Dental1,
  • Besma Aouar1,
  • Francoise Gondois-Rey1,
  • David Durantel1,
  • Thomas F Baumert1,
  • Jacques A Nunes1,
  • Daniel Olive1 and
  • Ivan Hirsch1
Retrovirology20129(Suppl 1):O5

https://doi.org/10.1186/1742-4690-9-S1-O5

Published: 25 May 2012

Introduction

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.

Materials and methods

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).

RESULTS

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.

Conclusions

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.

Authors’ Affiliations

(1)
Centre de Recherche en Cancérologie de Marseille

Copyright

© Stranska et al; licensee BioMed Central Ltd. 2012

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 (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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