Persistent Borna Disease Virus Infection Confers Instability of HSP70 mRNA in Glial Cells during Heat Stress
Persistent Borna Disease Virus Infection Confers Instability of HSP70 mRNA in Glial Cells during Heat Stress
复制标题
DOI：
10.1128/jvi.79.4.2033-2041.2005
复制
发表时间：
2005-02
影响因子：
5.4
通讯作者：
M. Yamashita;W. Kamitani;H. Yanai;Naohiro Ohtaki;Yohei Watanabe;Byeong-Jae Lee;S. Tsuji;K. Ikuta;K. Tomonaga
中科院分区：
文献类型：
--
作者：
M. Yamashita;W. Kamitani;H. Yanai;Naohiro Ohtaki;Yohei Watanabe;Byeong-Jae Lee;S. Tsuji;K. Ikuta;K. Tomonaga
博尔纳病病毒（Borna disease virus，BDV）是一种高度嗜神经的RNA病毒，可引起多种脊椎动物的神经系统疾病。虽然BDV容易建立持久的持久性，但持续感染的细胞在形态、活力和增殖方面保持明显正常的细胞表型。在这项研究中，为了了解BDV感染的应激反应的调节，我们研究了热休克蛋白（HSPs）在BDV持续感染的胶质细胞中的表达。有趣的是，我们发现，BDV的持久性并没有上调HSP 70的表达，即使在热应激处理的细胞。此外，在各种应激条件下，BDV感染的神经胶质细胞表现出快速变圆和从培养板脱离。免疫荧光分析表明，热应激快速破坏细胞骨架只有在持续感染的细胞，表明缺乏耐热性。有趣的是，我们发现，虽然持续感染的胶质细胞表达热休克蛋白70 mRNA后，热应激，其表达迅速消失在恢复期。这些结果表明，持续BDV感染可能会影响HSP70 mRNA的稳定性。最后，我们发现双链RNA依赖性蛋白激酶（PKR）在持续感染的细胞中以恒定的水平表达，无论是否有热休克。考虑到HSP 70和PKR产生之间的相互关系，我们的数据表明，BDV感染干扰细胞的应激反应，取消抗病毒活性和保持持久性。
ABSTRACT Borna disease virus (BDV) is a highly neurotropic RNA virus that causes neurological disorders in many vertebrate species. Although BDV readily establishes lasting persistence, persistently infected cells maintain an apparently normal cell phenotype in terms of morphology, viability, and proliferation. In this study, to understand the regulation of stress responses in BDV infection, we investigated the expression of heat shock proteins (HSPs) in glial cells persistently infected with BDV. Interestingly, we found that BDV persistence did not upregulate HSP70 expression even in cells treated with heat stress. Furthermore, BDV-infected glial cells exhibited rapid rounding and detachment from the culture plate under various stressful conditions. Immunofluorescence analysis demonstrated that heat stress rapidly disrupts the cell cytoskeleton only in persistently infected cells, suggesting a lack of thermotolerance. Intriguingly, we found that although persistently infected glial cells expressed HSP70 mRNA after heat stress, its expression rapidly disappeared during the recovery period. These observations indicated that persistent BDV infection may affect the stability of HSP70 mRNA. Finally, we found that the double-stranded RNA-dependent protein kinase (PKR) is expressed at a constant level in persistently infected cells with or without heat shock. Considering the interrelationship between HSP70 and PKR production, our data suggest that BDV infection disturbs the cellular stress responses to abolish antiviral activities and maintain persistence.