Comment in:

J Hepatol. 2004 Jan;40(1):184-6.

Science. 2003 May 16;300(5622):1100-1.

Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease.

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9048, USA.

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.

PMID: 12702807 [PubMed - indexed for MEDLINE]