Antiviral activity and RNA polyinerase degradation following Hsp90 inhibition in a range of negative strand viruses
Antiviral activity and RNA polyinerase degradation following Hsp90 inhibition in a range of negative strand viruses
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DOI：
10.1016/j.virol.2006.12.026
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发表时间：
2007-05-25
期刊：
影响因子：
3.7
通讯作者：
Lyles, Douglas S.
中科院分区：
文献类型：
--
作者：
Connor, John H.;McKenzie, Margie O.;Lyles, Douglas S.
我们已经分析了Hsp 90抑制剂在阻断负链RNA病毒复制中的有效性。在用原型负链病毒水泡性口炎病毒（VSV）感染的细胞中，抑制Hsp 90活性降低了在高和低感染复数下感染的细胞中的病毒复制。使用两种Hsp 90抑制剂格尔德霉素和根赤霉素观察到这种抑制。使用siRNA沉默Hsp 90表达也减少了病毒复制。Hsp 90抑制将新合成的L蛋白（VSV聚合酶的大亚基）的半衰期从>1小时改变为小于20分钟，而不影响其他VSV蛋白的稳定性。当格尔德霉素或根赤霉素加入到副粘病毒SV 5、HPIV-2、HPIV-3或SV 41感染的细胞或拉克罗斯本扬病毒感染的细胞中时，观察到病毒复制的抑制和病毒L蛋白的不稳定。基于这些结果，我们提出Hsp 90是对许多负链病毒复制重要的宿主因子（C）2007 Elsevier Inc. All rights reserved.
We have analyzed the effectiveness of Hsp90 inhibitors in blocking the replication of negative-strand RNA viruses. In cells infected with the prototype negative strand virus vesicular stomatitis virus (VSV), inhibiting Hsp90 activity reduced viral replication in cells infected at both high and low multiplicities of infection. This inhibition was observed using two Hsp90 inhibitors geldanamycin and radicicol. silencing of Hsp90 expression using siRNA also reduced viral replication. Hsp90 inhibition changed the half-life of newly synthesized L protein (the large subunit of the VSV polymerase) from >1 h to less than 20 min without affecting the stability of other VSV proteins. Both the inhibition of viral replication and the destabilization of the viral L protein were seen when either geldanamycin or radicicol was added to cells infected with paramyxoviruses SV5, HPIV-2, HPIV-3, or SV41, or to cells infected with the La Crosse bunyavirus. Based on these results, we propose that Hsp90 is a host factor that is important for the replication of many negative strand viruses (C) 2007 Elsevier Inc. All rights reserved.