Hsp90 inhibitors reduce influenza virus replication in cell culture

被引：138

作者：

Chase, Geoffrey ^{[1
]}

Deng, Tao ^{[2
,3
]}

Fodor, Ervin ^{[2
]}

Leung, Bo Wah ^{[2
]}

Mayer, Daniel ^{[1
]}

Schwemmle, Martin ^{[1
]}

Brownlee, George ^{[2
]}

机构：

[1] Univ Freiburg, Dept Virol, Inst Med Microbiol & Hyg, D-79104 Freiburg, Germany

[2] Univ Oxford, Sir William Dunn Sch Pathol, Chem Pathol Unit, Oxford OX1 3RE, England

[3] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China

来源：

VIROLOGY | 2008年 / 377卷 / 02期

基金：

英国医学研究理事会;

关键词：

influenza viruses replication; RNA polymerase; Hsp90; geldanamycin; 17; AAG; antiviral agents;

D O I：

10.1016/j.virol.2008.04.040

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：431 / 439

页数：9

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