✦ LIBER ✦

A new survival trick of hepatitis C virus: Blocking the activation of interferon regulatory factor-3

✍ Scribed by Markus H. Heim

Publisher: John Wiley and Sons
Year: 2003
Tongue: English
Weight: 105 KB
Volume: 38
Category: Article
ISSN: 0270-9139
DOI: 10.1002/hep.510380632

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✦ Synopsis

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.

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