Activation of anti-hepatitis C virus responses via Toll-like receptor 7

  • Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1828-33. doi: 10.1073/pnas.0510801103.
Jongdae Lee  1 ,  Christina C N Wu ,  Ki Jeong Lee ,  Tsung-Hsien Chuang ,  Kyoko Katakura ,  Yu-Tsueng Liu ,  Michael Chan ,  Rommel Tawatao ,  Michelle Chung ,  Carol Shen ,  Howard B Cottam ,  Michael M C Lai ,  Eyal Raz ,  Dennis A Carson
Affiliations
  • 1. Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0663, USA.
PMID: 16446426 DOI: 10.1073/pnas.0510801103
Abstract

IFN-alpha is used to suppress the replication of hepatitis C virus (HCV) in chronically infected patients with partial success. Here we present evidence showing that a ligand of Toll-like Receptor 7 (TLR7) can induce anti-HCV immunity not only by IFN induction, but also through an IFN-independent mechanism. Human hepatocyte line Huh-7 carrying an HCV replicon expressed TLR7, and activation of the receptor induced several Antiviral genes including IFN regulatory factor-7. Inhibitors of the enzyme Inosine monophosphate dehydrogenase augmented both IFN-dependent and -independent Antiviral effect. Prolonged exposure of Huh-7 cells to a TLR7 Ligand [SM360320 (9-benzyl-8-hydroxy-2-(2-methoxyethoxy)Adenine)], alone or in combination with an Inosine monophosphate dehydrogenase inhibitor, reduced HCV levels dose dependently. Immunohistochemical analysis of Livers shows that TLR7 is expressed in hepatocytes of normal or HCV-infected people. Because TLR7 agonists can impede HCV Infection both via type I IFN and independently of IFN, they may be considered as an alternative treatment of chronic HCV Infection, especially in IFN-alpha-resistant patients.

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