Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells

Nan Wang, Yuqiong Liang, Santhana Devaraj, Jie Wang, Stanley M. Lemon, Kui Li

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Toll-like receptor-3 (TLR3) senses double-stranded RNA, initiating signaling that activates NF-κB and interferon regulatory factor 3 (IRF-3), thereby inducing the synthesis of proinflammatory cytokines, type I interferons, and numerous interferon-stimulated genes (ISGs). This pathway has not been extensively investigated in human hepatocytes, and its role in sensing and protecting against hepatitis virus infections is uncertain. We show here that primary human hepatocytes express TLR3 and robustly upregulate ISGs upon poly(I·C) stimulation. We also show that TLR3 senses hepatitis C virus (HCV) infection when expressed in permissive hepatoma cells, acting independently of retinoic acid-inducible gene I and inducing IRF-3 activation and the synthesis of ISGs that restrict virus replication. In turn, HCV infection reduces the abundance of TRIF, an essential TLR3 adaptor, and impairs poly(I·C)-induced signaling. The induction and disruption of TLR3 signaling by HCV may be important factors in determining the outcome of infection and the ability of HCV to establish persistent infections.

Original languageEnglish (US)
Pages (from-to)9824-9834
Number of pages11
JournalJournal of Virology
Volume83
Issue number19
DOIs
StatePublished - Oct 1 2009

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Toll-Like Receptor 3
Hepatitis C virus
hepatoma
Hepacivirus
Antiviral Agents
Hepatocellular Carcinoma
interferons
Virus Diseases
Interferon Regulatory Factor-3
Interferons
polyinosinic-polycytidylic acid
infection
hepatocytes
Genes
cells
Hepatocytes
genes
Hepatitis Viruses
Interferon Type I
synthesis

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells. / Wang, Nan; Liang, Yuqiong; Devaraj, Santhana; Wang, Jie; Lemon, Stanley M.; Li, Kui.

In: Journal of Virology, Vol. 83, No. 19, 01.10.2009, p. 9824-9834.

Research output: Contribution to journalArticle

Wang, Nan ; Liang, Yuqiong ; Devaraj, Santhana ; Wang, Jie ; Lemon, Stanley M. ; Li, Kui. / Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells. In: Journal of Virology. 2009 ; Vol. 83, No. 19. pp. 9824-9834.
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