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Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1828-33. Epub 2006 Jan 30.

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

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  • 1Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0663, USA.

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.

PMID:
16446426
PMCID:
PMC1413670
DOI:
10.1073/pnas.0510801103
[PubMed - indexed for MEDLINE]
Free PMC Article
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