期刊
VIROLOGY
卷 377, 期 2, 页码 431-439出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2008.04.040
关键词
influenza viruses replication; RNA polymerase; Hsp90; geldanamycin; 17 AAG; antiviral agents
类别
资金
- Medical Research Council [G117/457, G9523972, G9826944, G9901312, G0700848] Funding Source: Medline
- MRC [G0700848, G9826944, G9523972, G117/457] Funding Source: UKRI
- Medical Research Council [G9826944, G9523972, G0700848, G117/457] Funding Source: researchfish
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.
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