Regulation of molecular chaperones by a human virus

描述（由申请人提供）：病毒复制需要宿主生物化学的重定向，以合成、折叠和组装病毒蛋白质，形成子代病毒体。虽然热休克蛋白（HSP）的表达和再分布已经在细胞热休克反应的背景下进行了广泛的研究，腺病毒感染的研究表明特异性HSP的选择性诱导。热休克基因似乎参与病毒感染，因为不能诱导热休克蛋白表达的病毒突变体是复制缺陷的，这种效应可以通过热休克或特异性热休克蛋白的异源表达来克服。为了阐明伴侣依赖病毒复制的分子基础，我们将确定和表征特异性热休克蛋白和伴侣网络诱导响应病毒复制，并检查HSF1转录因子在病毒特异性HSP基因诱导的贡献。使用RNA干扰方法，我们将研究这些分子伴侣对腺病毒复制的机制贡献。最后，我们建议建立伴侣招募网站的病毒复制和细胞蛋白质质量控制之间的关系，以更好地了解监管的伴侣依赖性功能的病毒。

DESCRIPTION (provided by applicant): Virus replication requires the redirection of host biochemistry to synthesize, fold and assemble viral proteins into progeny virions. While the expression and redistribution of heat shock proteins (HSPs) has been extensively studied in the context of the cellular heat shock response, studies on adenovirus infection demonstrate selective induction of specific HSPs. Heat shock genes appear to participate in virus infection as virus mutants incapable of inducing the expression of HSPs are replicative defective, an effect that can be overcome by heat shock or heterologous expression of specific HSPs. In order to elucidate the molecular basis for chaperone dependence of viral replication, we will identify and characterize the specific HSPs and chaperone networks induced in response to viral replication and examine the contribution of HSF1 transcription factor in viral specific HSP gene induction. Using an RNA interference approach, we will examine the mechanistic contribution of these chaperones to adenovirus replication. Finally, we propose to establish the relationship between chaperone recruitment to sites of virus replication and cellular protein quality control to better understand the regulation of chaperone-dependent functions by viruses.