[Effects of hepatitis C virus proteins on the interferon-stimulated signal transduction].
The mutation number in the interferon sensitivity determining region(ISDR) (aa2209-2248) in the nonstructural 5A(NS5A) region of hepatitis C virus(HCV) has been shown to correlate with the sensitivity of the virus to interferon treatment. To clearify this mechanism, the functions of the NS5A protein have extensively been studied. The NS5A protein has been shown to be phosphorylated. The NS5A protein 1) is a transactivator, 2) represses the expression of interferon-stimulated genes, 3) binds with PKR, an interferon-stimulated gene, and inhibits its activity, and 4) may inhibit interferon-induced apoptosis of HCV-infected hepatocytes. These effects of the NS5A are different depending on the ISDR types. The E2 protein also can bind with PKR and inhibits its activity. These mechanisms may explain the low responsiveness of HCV to interferon treatment and the difference in the sensitivity to interferon among the genotypes and ISDR types.
Sato
C
C
Department of Analytical Health Science, Tokyo Medical and Dental University.
D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology; D012324:RNA-Dependent RNA Polymerase
D007372:Interferons; D015534:Trans-Activators; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase