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


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.

SUBMITTER: Lee J 

PROVIDER: S-EPMC1413670 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature

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

Lee Jongdae J   Wu Christina C N CC   Lee Ki Jeong KJ   Chuang Tsung-Hsien TH   Katakura Kyoko K   Liu Yu-Tsueng YT   Chan Michael M   Tawatao Rommel R   Chung Michelle M   Shen Carol C   Cottam Howard B HB   Lai Michael M C MM   Raz Eyal E   Carson Dennis A DA  

Proceedings of the National Academy of Sciences of the United States of America 20060130 6


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  ...[more]

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