Formation of nuclear foci of the herpes simplex virus type 1 regulatory protein ICP4 at early times of infection: Localization, dynamics, recruitment of ICP27, and evidence for the De Novo induction of ND10-Like complexes
Formation of nuclear foci of the herpes simplex virus type 1 regulatory protein ICP4 at early times of infection: Localization, dynamics, recruitment of ICP27, and evidence for the De Novo induction of ND10-Like complexes
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DOI：
10.1128/jvi.78.4.1903-1917.2004
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发表时间：
2004-02-01
影响因子：
5.4
通讯作者：
Orr, A
中科院分区：
文献类型：
--
作者：
Everett, RD;Sourvinos, G;Orr, A
单纯疱疹病毒1型（HSV-1）与细胞核结构ND10或早幼粒细胞白血病蛋白（PML）核体有着复杂的联系。亲本病毒基因组最初与ND10并置，然后病毒复制区室从ND10相关基因组发育而来。病毒即时早期（IE）调节蛋白ICP0与ND10共定位，然后诱导ND10关键组分蛋白PML的降解，从而导致其他ND10蛋白的释放和扩散。IE转录调控蛋白ICP4也在感染早期形成病灶，其中许多与ND10并置于一起，随后发展成复制区室，这表明至少一些初始ICP4病灶包含亲本病毒基因组。在这里，我们报道了ICP4中心也含有ICP27，并且它们的形成在核膜内的位置发生得非常快。通过检查发展中的斑块或高多样性感染的薄粒细胞，我们发现证据表明，至少有一些nd10 -病毒核蛋白复合物的关联可归因于nd10样结构在响应传入病毒基因组时的新生形成。ICP4复合物在感染icp0 - 0突变病毒的细胞中以高而非低的多重性与ND10有效相关，蛋白酶体抑制剂MG132降低了这种关联程度。因此，病毒核蛋白复合物与ND10之间的相互作用部分是由于细胞的动态反应。这种反应是由功能性ICP0调节的，在没有功能性ICP0的情况下，细胞是生产性感染还是非生产性感染，可以通过ICP4病灶和ND10蛋白的相对位置来区分。
Herpes simplex virus type 1 (HSV-1) has an intricate association with cellular nuclear structures known as ND10 or promyelocytic leukemia protein (PML) nuclear bodies. Parental viral genomes initially become juxtaposed to ND10, and then viral replication compartments develop from the ND10-associated genomes. Viral immediate-early (IE) regulatory protein ICP0 colocalizes with ND10 and then induces the degradation of critical ND10 component protein PML and therefore the release and dispersal of other ND10 proteins. The IE transcriptional regulatory protein ICP4 also forms foci at early times of infection, many of which are juxtaposed to ND10 and later develop into replication compartments, indicating that at least some of the initial ICP4 foci contain parental viral genomes. Here we report that the ICP4 foci also contain ICP27 and that their formation occurs extremely rapidly at locations just inside the nuclear envelope. By examining developing plaques or thinly seeded cells infected at high multiplicity, we found evidence to suggest that at least some of the ND10-viral nucleoprotein complex association could be attributed to de novo formation of ND10-like structures in response to incoming viral genomes. The ICP4 complexes associated efficiently with ND10 in cells infected with an ICP0-null mutant virus at high but not at low multiplicity, and the degree of association was reduced by the proteasome inhibitor MG132. Therefore, the interaction between viral nucleoprotein complexes and ND10 is in part due to a dynamic response by the cell. This response is modulated by functional ICP0, and cells that are productively or nonproductively infected in the absence of functional ICP0 can be distinguished by the relative locations of ICP4 foci and ND10 proteins.