Expression of Hepatitis C Virus Ns5a Natural Mutants in A Hepatocytic Cell Line Inhibits the Antiviral Effect of Interferon in A Pkr–Independent Manner

• DOI: 10.1053/jhep.2001.24749
• Publication Date: 2002-08-25T03:46:10Z
• Authors: Philippe Podevin; Abdelmajid Sabile; Rodrigo Gajardo; Nadira Delhem; Annie Abadie; Pierre-Yves Lozach; Laura Beretta; Christian Bréchot
• Keywords: NS5A; Protein kinase R; Immunoprecipitation; Viability assay; Antiviral protein

The impact of hepatitis C virus NS5A protein mutations on interferon alfa (IFN-alpha) signaling pathway, cell proliferation, and viability is an important issue that still under debate. We have therefore combined transient stable expression in a human hepatocytic line (Huh7) 3 full-length sequences, isolated from patients with or without response to IFN-alpha therapy. Expression all NS5A-reduced global antiviral activity both vesicular stomatitis (VSV) encephalomyocarditis (EMCV) replication. did not show, however, effect these proteins double-stranded RNA-dependent kinase (PKR) as well colocalization coimmunoprecipitation between PKR. also failed show the mutants tested proliferation viability. Overall, our results support role controlling activity; they PKR-independent mechanisms are implicated, at least liver-derived cells.