In trans interaction of hepatitis C virus helicase domains mediates protease activity critical for internal NS3 cleavage and cell transformation

Pan, Ren-You; Hung, Tzu-Min; Kou, Yi-Hen; Chan, Nei-Li; Chang, Ming-Fu; Chang, Shin C.

doi:10.1016/j.febslet.2009.11.090

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Volume 584, Issue 3 , Pages 482-486, 5 February 2010

In trans interaction of hepatitis C virus helicase domains mediates protease activity critical for internal NS3 cleavage and cell transformation

Edited by Hans-Dieter Klenk

Ren-You Pan
- Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
Tzu-Min Hung
- Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan
Yi-Hen Kou
- Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
Nei-Li Chan
- Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan
Ming-Fu Chang
- Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan
Shin C. Chang
- Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
- Corresponding author. Address: Institute of Microbiology, National Taiwan University College of Medicine, No. 1, Jen-Ai Road, First Section, Taipei 100, Taiwan. Fax: +886 2 23915293.

Received 9 October 2009; received in revised form 19 November 2009; accepted 26 November 2009. published online 01 December 2009.

Abstract

Hepatitis C virus (HCV) internal non-structural protein 3 (NS3) cleavage can occur in trans in the presence of NS4A. In this study, we have further demonstrated a critical role of the helicase domain in the internal NS3 cleavage, different from HCV polyprotein processing which requires only the serine protease domain. The NTPase domain of NS3 helicase interacts with the RNA binding domain to facilitate internal NS3 cleavage. In addition, NS3 protease activity contributes to the transforming ability of the major internal cleavage product NS3(1–402). These findings imply important roles of the internal cleavage and protease activity of the NS3 protein in the pathogenesis of HCV.