|
pubmed:abstractText |
The effect of six drugs (amantadine, glycyrrhizin, ribavirin, ursodeoxycholic acid, alcohol, and IFN) on HAV RNA translation from the HAV internal ribosomal entry site (IRES) was investigated using a bicistronic reporter construct containing HAV IRES as intragenic spacer. Huh-7 cells and derivatives were transfected with in vitro transcripts, and the reporter gene activity was determined. IFN suppressed both cap-dependent and HAV IRES-dependent translation, while amantadine specifically inhibited HAV IRES-dependent translation. In contrast to IFN, by reporter assay, amantadine did not activate the interferon-stimulated response element (ISRE) or interferon gamma-activated sequence (GAS)-associated pathways. Immunoblot analysis revealed that amantadine had no effect on PKR and on IFN-regulatory factor-1 (IRF-1) expression. These findings demonstrated a novel antiviral effect of amantadine against HAV with or without HCV infection.
|
|
pubmed:affiliation |
Safety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522, Japan. kandat-cib@umin.ac.jp
|
