Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase

被引：373

作者：

Watashi, K ^{[1
]}

Ishii, N ^{[1
]}

Hijikata, M ^{[1
]}

Inoue, D ^{[1
]}

Murata, T ^{[1
]}

Miyanari, Y ^{[1
]}

Shimotohno, K ^{[1
]}

机构：

[1] Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Lab Human Tumor Viruses, Kyoto 6068507, Japan

来源：

MOLECULAR CELL | 2005年 / 19卷 / 01期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/j.molcel.2005.05.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPlase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus (HCV) genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.

引用

页码：111 / 122

页数：12

共 48 条

[1] Characterization of the hepatitis C virus RNA replication complex associated with lipid rafts [J].

Aizaki, H ;

Lee, KJ ;

Sung, VMH ;

Ishiko, H ;

Lai, MMC .

VIROLOGY, 2004, 324 (02) :450-461

[2] Novel cell culture systems for the hepatitis C virus [J].

Bartenschlager, R ;

Lohmann, V .

ANTIVIRAL RESEARCH, 2001, 52 (01) :1-17

[3] MODE OF ACTION OF SDZ NIM-811, A NONIMMUNOSUPPRESSIVE CYCLOSPORINE-A ANALOG WITH ACTIVITY AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 - INTERFERENCE WITH HIV PROTEIN-CYCLOPHILIN-A INTERACTIONS [J].

BILLICH, A ;

HAMMERSCHMID, F ;

PEICHL, P ;

WENGER, R ;

ZENKE, G ;

QUESNIAUX, V ;

ROSENWIRTH, B .

JOURNAL OF VIROLOGY, 1995, 69 (04) :2451-2461

[4] Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells [J].

Braaten, D ;

Luban, J .

EMBO JOURNAL, 2001, 20 (06) :1300-1309

[5] IDENTIFICATION OF THE IMMUNOPHILINS CAPABLE OF MEDIATING INHIBITION OF SIGNAL-TRANSDUCTION BY CYCLOSPORINE-A AND FK506 - ROLES OF CALCINEURIN BINDING AND CELLULAR LOCATION [J].

BRAM, RJ ;

HUNG, DT ;

MARTIN, PK ;

SCHREIBER, SL ;

CRABTREE, GR .

MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (08) :4760-4769

[6] Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A [J].

Brazin, KN ;

Mallis, RJ ;

Fulton, DB ;

Andreotti, AH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) :1899-1904

[7] Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk [J].

Colgan, J ;

Asmal, M ;

Neagu, M ;

Yu, B ;

Schneidkraut, J ;

Lee, Y ;

Sokolskaja, E ;

Andreotti, A ;

Luban, J .

IMMUNITY, 2004, 21 (02) :189-201

[8] A cyclophilin function in Hsp90-dependent signal transduction [J].

Duina, AA ;

Chang, HCJ ;

Marsh, JA ;

Lindquist, S ;

Gaber, RF .

SCIENCE, 1996, 274 (5293) :1713-1715

[9] Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex [J].

Egger, D ;

Wölk, B ;

Gosert, R ;

Bianchi, L ;

Blum, HE ;

Moradpour, D ;

Bienz, K .

JOURNAL OF VIROLOGY, 2002, 76 (12) :5974-5984

[10] Replication of hepatitis C virus RNA occurs in a membrane-bound replication complex containing nonstructural viral proteins and RNA [J].

El-Hage, N ;

Luo, GX .

JOURNAL OF GENERAL VIROLOGY, 2003, 84 :2761-2769

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