Stimulation of Hepatitis C Virus (HCV) Nonstructural Protein 3 (NS3) Helicase Activity by the NS3 Protease Domain and by HCV RNA-Dependent RNA Polymerase

• DOI: 10.1128/jvi.79.14.8687-8697.2005
• Publication Date: 2005-07-01T06:29:34Z
• Authors: Chen Zhang; Zhaohui Cai; Young-Chan Kim; Ranjith Kumar; Fenghua Yuan; Pei-Yong Shi; Cheng Kao; Guangxiang Luo
• Keywords: NS3; NS5B; RNA Helicase A

ABSTRACT Hepatitis C virus (HCV) nonstructural protein 3 (NS3) possesses multiple enzyme activities. The N-terminal one-third of NS3 primarily functions as a serine protease, while the remaining two-thirds serve helicase and nucleoside triphosphatase. Whether activities are functionally interdependent and/or modulated by other viral NS proteins remains unclear. We performed biochemical studies to examine functional interdependence protease domains modulation NS5B, an RNA-dependent RNA polymerase (RdRp). found that domain full-length (NS3FL) enhances activity. Additionally, HCV RdRp stimulates NS3FL activity more than sevenfold. However, was unaffected RdRp. Glutathione S -transferase pull-down well fluorescence anisotropy results revealed is required for specific NS5B interaction. These findings suggest regulates during replication. In contrast, does not increase in vitro, which contrary previously published report