Hepatitis C virus NS5A protein modulates template selection by the RNA polymerase in in vitro system

Ivanov, Alexander V.; Tunitskaya, Vera L.; Ivanova, Olga N.; Mitkevich, Vladimir A.; Prassolov, Vladimir S.; Makarov, Alexander A.; Kukhanova, Marina K.; Kochetkov, Sergey N.

doi:10.1016/j.febslet.2008.12.016

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Volume 583, Issue 2 , Pages 277-280, 22 January 2009

Hepatitis C virus NS5A protein modulates template selection by the RNA polymerase in in vitro system

Edited by Hans-Dieter Klenk

Alexander V. Ivanov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia
- University of Oslo, Centre for Medical Study in Russia, Moscow 119334, Russia
- Corresponding author. Address: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, MODFAS, Vavilov Strasse, 32, Moscow 119991, Russia. Fax: +7 499 1351405.
Vera L. Tunitskaya
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia
Olga N. Ivanova
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia
Vladimir A. Mitkevich
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia
- University of Oslo, Centre for Medical Study in Russia, Moscow 119334, Russia
Vladimir S. Prassolov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia
Alexander A. Makarov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia
Marina K. Kukhanova
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia
Sergey N. Kochetkov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov street, 32, Moscow 119991, Russia

Received 30 July 2008; received in revised form 27 November 2008; accepted 5 December 2008. published online 15 December 2008.

Abstract

Hepatitis C virus (HCV) NS5A phosphoprotein is a component of virus replicase. Here we demonstrate that in vitro unphosphorylated NS5A protein inhibits HCV RNA-dependent RNA polymerase (RdRp) activity in polyA–oligoU system but has little effect on synthesis of viral RNA. The phosphorylated casein kinase (CK) II NS5A protein causes the opposite effect on RdRp in each of these systems. The phosphorylation of NS5A protein with CKII does not affect its affinity to the HCV RdRp and RNA. The NS5A phosphorylation with CKI does not change the RdRp activity. Herein we report evidence that the NS5A prevents template binding to the RdRp.