Hsp90 inhibitors reduce influenza virus replication in cell culture
Hsp90 inhibitors reduce influenza virus replication in cell culture
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DOI：
10.1016/j.virol.2008.04.040
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发表时间：
2008-08-01
期刊：
影响因子：
3.7
通讯作者：
Brownlee, George
中科院分区：
文献类型：
--
作者：
Chase, Geoffrey;Deng, Tao;Brownlee, George
甲型流感病毒的病毒RNA聚合酶复合体由PB1、PB2和PA三个亚基组成。最近，细胞伴侣Hsp90被证明通过与PB1和PB2结合而在核输入和三聚体聚合酶复合体的组装中发挥作用。在这里，我们展示了Hsp90抑制剂，格尔达霉素或其衍生物17-AAG，在细胞培养中延缓流感病毒的生长，导致感染早期病毒滴度下降1-2个对数。我们认为这是由于PB1和PB2的半衰期缩短以及PB1和PA的核进口受到抑制而导致病毒RNP组装减少所致。HSP90抑制剂可能代表了一类新的抗流感病毒化合物。(C)2008 Elsevier Inc.保留所有权利。
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.