The Stimulatory Mechanism of Hepatitis C Virus NS5A Protein on the NS5B Catalyzed Replication Reaction In Vitro

Elizabeth M Quezada 1, 2, Caroline M Kane 1, *
1 Department of Molecular and Cell Biology, University of California, Berkeley CA 94720-3202, USA
2 Stowers Research Institute 1000 East 50th Street Kansas City, MO 64110, USA

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© Quezada and Kane; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Molecular and Cell Biology, 34 Koshland Hall, University of California, Berkeley, CA 94720-3202, USA; Tel: 510-642-4118; E-mail:


The Hepatitis C Virus RNA dependent RNA polymerase, NS5B, is stimulated by the NS5A protein in vitro. To explore this stimulatory mechanism, we compared the activity of a mutant of NS5B containing a deletion of the β-loop region with that of the full length NS5B in response to NS5A. While the NS5A protein does stimulate full length NS5B, NS5A does not stimulate the NS5B deletion mutant during either replication initiation or elongation. This result suggests that the activation mechanism might involve a NS5A-mediated conformational change of the β-loop of NS5B. Such a conformational change would be predicted to prevent steric clash of the RNA template and newly synthesized RNA product. Consistent with this hypothesis, RNA binding is enhanced when the full length NS5B and NS5A are incubated with RNA, but RNA binding is unchanged with incubation of NS5A and the NS5B β-loop deletion mutant.

Keywords: Hepatitis C virus, NS5A, NS5B, regulation.