Double-stranded RNA-activated protein kinase inhibits hepatitis C virus replication but may be not essential in interferon treatment.

Background: Double-stranded RNA-activated protein kinase (PKR), an interferon (IFN)-stimulated gene, is activated by binding with double-stranded RNA, a putative replicative intermediate of the hepatitis C virus (HCV). Activated PKR phosphorylates the alpha subunit of eukaryotic initiation factor-2 to inhibit the translation of viral protein.

Aims/methods: We established stable PKR knockdown Huh7 cells using RNA interference and investigated the effect of PKR against HCV replication using a subgenomic replicon that expressed luciferase reporter protein and the JFH1 full-length HCV genome.

Polymorphism of OAS-1 determines liver fibrosis progression in hepatitis C by reduced ability to inhibit viral replication.

Background: Progression of disease after hepatitis C virus (HCV) infection differs among individuals, indicating a possibility of participation of host genetic factors. 2'-5'-oligoadenylate synthetase 1 (OAS-1), an important component of the innate immune system, has an antiviral function, and may therefore have a certain relationship with progression of disease.

Aim: To evaluate single nucleotide polymorphisms (SNPs) of OAS-1 and its relationship with the disease status of HCV infection.

Association of interferon regulatory factor-7 gene polymorphism with liver cirrhosis in chronic hepatitis C patients.

Background And Aims: Interferon (IFN) regulatory factor 7 (IRF-7) has been shown to play an essential role in the transcriptional activation of virus-inducible cellular genes, especially IFN genes. Polymorphisms of the IRF-7 gene may probably affect both the quality and the quantity of IRF-7. We investigated the role of IRF-7 polymorphisms in Japanese patients with chronic hepatitis C virus (HCV) infection.

Potential contribution of tumor suppressor p53 in the host defense against hepatitis C virus.

Unlabelled: Infection by hepatitis C virus (HCV) usually results into chronic hepatitis that can ultimately lead to cirrhosis and hepatocellular carcinoma. Type 1 interferons (IFN-alpha/beta) constitute the primary cellular defense against viral infection including HCV. IFN binding to their receptors activates associated Jak1 and Tyk2 kinases, which ultimately leads to phosphorylation and assembly of a signal transducer and activator of transcription protein (STAT)1-STAT2-interferon regulatory factor (IRF)9 trimetric complex called interferon-stimulated gene factor 3 that translocates into the nucleus and binds to the interferon- stimulated response elements (ISRE), leading to transcriptional induction of several antiviral genes, including double-stranded RNA-activated protein kinase (PKR), 2',5'- oligoadenylate synthetase (OAS), and myxovirus resistance protein A (MxA).