Formation of aggresome-like structures in herpes simplex virus type 2-infected cells and a potential role in virus assembly.
Formation of aggresome-like structures in herpes simplex virus type 2-infected cells and a potential role in virus assembly.
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DOI：
10.1016/j.yexcr.2004.06.010
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发表时间：
2004-10
影响因子：
3.7
通讯作者：
N. Nozawa;Y. Yamauchi;K. Ohtsuka;Y. Kawaguchi;Y. Nishiyama
中科院分区：
文献类型：
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作者：
N. Nozawa;Y. Yamauchi;K. Ohtsuka;Y. Kawaguchi;Y. Nishiyama
单纯疱疹病毒(HSV)是一种大的包膜DNA病毒，可在细胞核内复制，并组装在细胞质中形成成熟的感染性病毒粒子。在这项研究中，我们提出了证据，在HSV-2感染的细胞中，一些被膜蛋白(UL46和VP16)和新合成的核衣壳积累在与侵袭体具有相同特征的核旁区域，即对错误折叠的蛋白质做出反应而形成的细胞结构[J.Cell Biol]。146(1999)1239，J.Cell Biol.143(1998)2010年]。HSV-2感染诱导的邻近核区(侵袭体结构)定位于微管组织中心(MTOC)，聚集线粒体、高尔基体衍生的小泡以及热休克蛋白(HSP)40和HSP70等细胞伴侣。微管解离药物诺康唑可阻断侵袭体结构的形成，提示在HSV-2感染细胞中，微管依赖的转运可能参与了病毒和细胞蛋白在这些部位的积聚。这些特征与支配侵略体形成的特征相似。然而，与侵袭体相反，在HSV-2感染的细胞中，没有观察到围绕MTOC的波形蛋白笼具有侵袭体样结构，这些结构的维持需要完整的微管网络。诺可达唑对侵袭体结构的破坏导致了对细胞内感染颗粒产生的低但一致的影响(减少了10倍)。这些结果表明，侵袭体样结构在HSV-2复制中不起关键作用，但起增强作用。
Herpes simplex virus (HSV) is a large, enveloped DNA virus that replicates in the nucleus and is assembled in the cytoplasm to the mature infectious virion. In this study, we present evidence that, in HSV-2-infected cells, some tegument proteins (UL46 and VP16) and newly synthesized nucleocapsids accumulate in a juxtanuclear domain sharing characteristics with aggresomes, cellular structures formed in response to misfolded proteins [J. Cell Biol. 146 (1999) 1239, J. Cell Biol. 143 (1998) 2010]. The juxtanuclear domains (aggresome-like structures) induced by HSV-2 infection localize to the microtubule organizing center (MTOC) where the clustering mitochondria, Golgi-derived vesicles, and cellular chaperones including heat shock protein (Hsp)40 and Hsp70 were recruited. Formation of aggresome-like structures was blocked by the presence of microtubule-disassembling drug nocodazole, indicating that microtubule-dependent transport may be involved in the accumulation of viral and cellular proteins at these sites in HSV-2-infected cells. These features are similar to those governing the formation of aggresomes. In contrast to aggresomes, however, the vimentin cage surrounding the MTOC was not observed with the aggresome-like structures in HSV-2-infected cells, and the maintenance of these structures required an intact microtubular network. Disruption of the aggresome-like structures by nocodazole treatment led to a low but consistent effect (10-fold decrease) on the production of intracellular infectious particles. These results suggest that aggresome-like structures do not play a critical but augmentary role in HSV-2 replication.