Herpes simplex virus type 1 DNA polymerase requires the mammalian chaperone Hsp90 for proper localization to the nucleus
Herpes simplex virus type 1 DNA polymerase requires the mammalian chaperone Hsp90 for proper localization to the nucleus
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DOI：
10.1128/jvi.79.16.10740-10749.2005
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发表时间：
2005-08-01
影响因子：
5.4
通讯作者：
Weller, SK
中科院分区：
文献类型：
--
作者：
Burch, AD;Weller, SK
许多病毒和噬菌体利用伴侣系统进行DNA复制和病毒形态发生。我们先前已经证明，在单纯疱疹病毒1型(HSV-1)感染的细胞核中，富含Hsp70/Hsp40伴侣机制的病灶形成于病毒复制隔间附近(A.D.Burch和S.K.Weller，J.Virol)。78：7175-7185,2004)。这些疫源地现在被命名为病毒诱导的伴侣蛋白富集型(副)疫源地。由于Hsp90分子伴侣机制在真核生物中参与了Hsp70/Hsp40系统，因此对Hsp90在HSV-1感染细胞中的亚细胞定位进行了分析。HSP90存在于病毒复制隔间以及HSP70/HSP40富集灶中。Hsp90的抑制剂格尔达那霉素会导致HSV-1产量下降，并阻止病毒DNA的合成。此外，我们还发现，在格尔达霉素存在的情况下，病毒DNA聚合酶在感染细胞和转基因细胞中都错误定位于细胞质。此外，在Hsp90抑制剂存在的情况下，通过Western印迹分析检测到病毒聚合酶依赖于蛋白酶体的降解。这些数据表明，HSV-1聚合酶可能是Hsp90伴侣系统的客户蛋白。这种关联的干扰似乎导致病毒聚合酶的降解、异常折叠和/或细胞内定位。
Many viruses and bacteriophage utilize chaperone systems for DNA replication and viral morphogenesis. We have previously shown that in the herpes simplex virus type 1 (HSV-1) -infected cell nucleus, foci enriched in the Hsp70/Hsp40 chaperone machinery are formed adjacent to viral replication compartments (A. D. Burch and S. K. Weller, J. Virol. 78:7175-7185, 2004). These foci have now been named virus-induced chaperone-enriched (VICE) foci. Since the Hsp90 chaperone machinery is known to engage the Hsp70/Hsp40 system in eukaryotes, the subcellular localization of Hsp90 in HSV-1-infected cells was analyzed. Hsp90 is found within viral replication compartments as well as in the Hsp70/Hsp40-enriched foci. Geldanamycin, an inhibitor of Hsp90, results in decreased HSV-1 yields and blocks viral DNA synthesis. Furthermore, we have found that the viral DNA polymerase is mislocalized to the cytoplasm in both infected and transfected cells in the presence of geldanamycin. Additionally, in the presence of an Hsp90 inhibitor, proteasome-dependent degradation of the viral polymerase was detected by Western blot analysis. These data identify the HSV-1 polymerase as a putative client protein of the Hsp90 chaperone system. Perturbations in this association appear to result in degradation, aberrant folding, and/or intracellular localization of the viral polymerase.