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Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease RID B-2279-2011

Author:
Foy, E  Li, K  Wang, CF  Sumpter, R  Ikeda, M  Lemon, SM  Gale, M  


Journal:
SCIENCE


Issue Date:
2003


Abstract(summary):

Persistent infections with hepatitis C virus (HCV) are likely to depend on viral inhibition of host defenses. We show that the HCV NS3/4A serine protease blocks the phosphorylation and effector action of interferon regulatory factor -3 (IRF-3), a key cellular antiviral signaling molecule. Disruption of NS3/4A protease function by mutation or a ketoamide peptidomimetic inhibitor relieved this blockade and restored IRF-3 phosphorylation after cellular challenge with an unrelated virus. Furthermore, dominant-negative or constitutively active IRF-3 mutants, respectively, enhanced or suppressed HCV RNA replication in hepatoma cells. Thus, the NS3/4A protease represents a dual therapeutic target, the inhibition of which may both block viral replication and restore IRF-3 control of HCV infection.


Page:
1145---1148


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