Effect of protease and helicase mutations on HCV NS3 activity

被引:2
作者
Eisa, Zaki Monawar [1 ]
机构
[1] King Fahad Cent Hosp, Jazan, Saudi Arabia
关键词
Hepatitis C virus (HCV); Non structural 3 (NS3); C VIRUS POLYPROTEIN; HEPATITIS-C; SERINE-PROTEASE; INTERFERON; CLEAVAGE; INHIBITION; EXPRESSION;
D O I
10.1016/j.sjbs.2010.09.001
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hepatitis C virus (HCV) causes serious infections in the liver which may lead to liver cirrhosis and hepatocellular carcinoma. Non structural 3 (NS3) protein is one of the most important proteins of the virus which has protease and helicase activities. Protease activity has a crucial role in the replication and persistence of the virus. Site directed mutation was carried out in the protease region of one NS3 and another site directed mutation in the helicase region of another NS3. The expression of both mutated NS3 was compared with wild NS3. Expression of the three different NS3 types was confirmed by in situ staining and western blotting using an anti-NS3 antibody and correlated with a reduced antiviral response after treatment with interferon-alpha. Mutation analysis showed that the NS3 protease activity and not the NS3 helicase was essential for the inhibition of the interferon-alpha response. (C) 2011 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.
引用
收藏
页码:195 / 200
页数:6
相关论文
共 19 条
[1]   KINETIC AND STRUCTURAL-ANALYSES OF HEPATITIS-C VIRUS POLYPROTEIN PROCESSING [J].
BARTENSCHLAGER, R ;
AHLBORNLAAKE, L ;
MOUS, J ;
JACOBSEN, H .
JOURNAL OF VIROLOGY, 1994, 68 (08) :5045-5055
[2]   Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKε [J].
Breiman, A ;
Grandvaux, N ;
Lin, RT ;
Ottone, C ;
Akira, S ;
Yoneyama, M ;
Fujita, T ;
Hiscott, J ;
Meurs, EF .
JOURNAL OF VIROLOGY, 2005, 79 (07) :3969-3978
[3]   The scientific challenge of hepatitis C [J].
Cohen, J .
SCIENCE, 1999, 285 (5424) :26-30
[4]  
Errington W, 1999, J MED VIROL, V59, P456, DOI 10.1002/(SICI)1096-9071(199912)59:4<456::AID-JMV6>3.0.CO
[5]  
2-0
[6]   Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling [J].
Foy, E ;
Li, K ;
Sumpter, R ;
Loo, YM ;
Johnson, CL ;
Wang, CF ;
Fish, PM ;
Yoneyama, M ;
Fujita, T ;
Lemon, SM ;
Gale, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (08) :2986-2991
[7]   Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease [J].
Foy, E ;
Li, K ;
Wang, CF ;
Sumpter, R ;
Ikeda, M ;
Lemon, SM ;
Gale, M .
SCIENCE, 2003, 300 (5622) :1145-1148
[8]   2 RELATED SUPERFAMILIES OF PUTATIVE HELICASES INVOLVED IN REPLICATION, RECOMBINATION, REPAIR AND EXPRESSION OF DNA AND RNA GENOMES [J].
GORBALENYA, AE ;
KOONIN, EV ;
DONCHENKO, AP ;
BLINOV, VM .
NUCLEIC ACIDS RESEARCH, 1989, 17 (12) :4713-4730
[9]   CHARACTERIZATION OF THE HEPATITIS-C VIRUS-ENCODED SERINE PROTEINASE - DETERMINATION OF PROTEINASE-DEPENDENT POLYPROTEIN CLEAVAGE SITES [J].
GRAKOUI, A ;
MCCOURT, DW ;
WYCHOWSKI, C ;
FEINSTONE, SM ;
RICE, CM .
JOURNAL OF VIROLOGY, 1993, 67 (05) :2832-2843
[10]   POLY(U) BINDING-ACTIVITY OF HEPATITIS-C VIRUS NS3 PROTEIN, A PUTATIVE RNA HELICASE [J].
KANAI, A ;
TANABE, K ;
KOHARA, M .
FEBS LETTERS, 1995, 376 (03) :221-224