Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein
Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein
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DOI：
10.1128/jvi.75.18.8697-8711.2001
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发表时间：
2001-09-01
影响因子：
5.4
通讯作者：
Blaho, JA
中科院分区：
文献类型：
--
作者：
Kotsakis, A;Pomeranz, LE;Blaho, JA
全长VP22是1型单纯疱疹病毒（HSV-1）在生产感染过程中在细胞间有效传播所必需的。VP22是一种病毒粒子磷酸化蛋白，在同步感染过程中，其核定位开始于感染后5 ~ 7小时。本研究的目的是确定HSV-1感染的哪些特征能够调节VP22进入细胞核的易位。我们报道如下。(i) HSV-1 (F)诱导的微管重排发生在13 hpi感染的Vero细胞中，其特征是明显的微管组织中心（MtOCs）的丢失。在25 hpi处检测到改造后的MtOCs。（ii） VP22在细胞微管重排前存在于细胞质中，重排后存在于细胞核中。（iii）通过添加紫杉醇来稳定微管，无论是在感染期间还是在缺乏其他病毒蛋白的情况下，表达VP22的细胞中，都增加了VP22在细胞质中的积累。（iv）在微管解聚剂nocodazole处理的细胞中，VP22定位于细胞核，紫杉醇或nocodazole处理均可阻止HSV-I(F)在Vero细胞中的最佳复制。(v) VP22向细胞核的迁移发生在磷酸乙酸存在的情况下，这表明病毒DNA和真正的晚期蛋白质合成并不需要它的易位。基于这些结果，我们得出结论：（iv） HSV-1感染过程中的微管重组促进了VP22的核定位。
Full-length VP22 is necessary for efficient spread of herpes simplex virus type 1 (HSV-1) from cell to cell during the course of productive infection. VP22 is a virion phosphoprotein, and its nuclear localization initiates between 5 and 7 h postinfection (hpi) during the course of synchronized infection. The goal of this study was to determine which features of HSV-1 infection function to regulate the translocation of VP22 into the nucleus. We report the following. (i) HSV-1 (F)-induced microtubule rearrangement occurred in infected Vero cells by 13 hpi and was characterized by the loss of obvious microtubule organizing centers (MtOCs). Reformed MtOCs were detected at 25 hpi. (ii) VP22 was observed in the cytoplasm of cells prior to microtubule rearrangement and localized in the nucleus following the process. (iii) Stabilization of microtubules by the addition of taxol increased the accumulation of VP22 in the cytoplasm either during infection or in cells expressing VP22 in the absence of other viral proteins. (iv) While VP22 localized to the nuclei of cells treated with the microtubule depolymerizing agent nocodazole, either taxol or nocodazole treatment prevented optimal HSV-I(F) replication in Vero cells. (v) VP22 migration to the nucleus occurred in the presence of phosphonoacetic acid, indicating that viral DNA and true late protein synthesis were not required for its translocation. Based on these results, we conclude that (iv) microtubule reorganization during HSV-1 infection facilitates the nuclear localization of VP22.