Characterization of HCV interactions with Toll-like receptors and RIG-I in liver cells

PLoS One. 2011;6(6):e21186. doi: 10.1371/journal.pone.0021186. Epub 2011 Jun 17.


Background and aim: The aim of this study was to examine the mechanisms of IFN induction and viral escape. In order to accomplish the goal we compared our new hepatoma cell line LH86, which has intact TLR3 and RIG-I expression and responds to HCV by inducing IFN, with Huh7.5 cells which lack those features.

Methods: The initial interaction of LH86 cells, Huh7.5 cells or their transfected counter parts (LH86 siRIG-I, siTLR3 or siTLR7 and Huh7.5 RIG-I, TLR3 or TLR7) after infection with HCV (strain JFH-1) was studied by measuring the expression levels of IFNβ, TRAIL, DR4, DR5 and their correlation to viral replication.

Results: HCV replicating RNA induces IFN in LH86 cells. The IFN induction system is functional in LH86, and the expression of the RIG-I and TLR3 in LH86 is comparable to the primary hepatocytes. Both proteins appear to play important roles in suppression of viral replication. We found that innate immunity against HCV is associated with the induction of apoptosis by RIG-I through the TRAIL pathway and the establishment of an antiviral state by TLR3. HCV envelope proteins interfere with the expression of TLR3 and RIG-I.

Conclusion: These findings correlate with the lower expression level of PRRs in HCV chronic patients and highlight the importance of the PRRs in the initial interaction of the virus and its host cells. This work represents a novel mechanism of viral pathogenesis for HCV and demonstrates the role of PRRs in viral infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Death / drug effects
  • Cell Line, Tumor
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Down-Regulation / drug effects
  • Hepacivirus / drug effects
  • Hepacivirus / metabolism
  • Hepacivirus / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Interferon-beta / pharmacology
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / virology*
  • Protein Binding / drug effects
  • Signal Transduction / drug effects
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*
  • Viral Envelope Proteins / metabolism
  • Virus Replication / drug effects


  • TNF-Related Apoptosis-Inducing Ligand
  • Toll-Like Receptors
  • Viral Envelope Proteins
  • Interferon-beta
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases