Herpes simplex virus type 1 ICP0 protein does not accumulate in the nucleus of primary neurons in culture
Herpes simplex virus type 1 ICP0 protein does not accumulate in the nucleus of primary neurons in culture
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DOI：
10.1128/jvi.74.21.10132-10141.2000
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发表时间：
2000-11-01
影响因子：
5.4
通讯作者：
Fink, DJ
中科院分区：
文献类型：
--
作者：
Chen, XP;Li, J;Fink, DJ
疱疹细胞蛋白0（ICP 0）是单纯疱疹病毒（HSV）即刻早期（IE）α 0基因的产物，是病毒早期（E）和晚期（L）基因表达的混杂反式激活因子。缺乏ICP 0功能的HSV突变体在病毒生长和蛋白质合成方面严重缺陷，特别是在低感染复数下。在体外感染过程的早期，ICP 0蛋白在细胞核内的不同结构域中积累，形成在病毒基因转录中具有活性的特征结构。然而，在用仅表达ICP 0的重组HSV突变体体外感染原代三叉神经节细胞后，我们观察到ICP 0蛋白仅在雪旺细胞的核中以特征性核内分布积累;尽管在这些细胞中表达ICP 0 RNA，但培养物中的神经元没有积累ICP 0。在分化为神经元表型的PC 12细胞中也观察到了同样的现象。在培养的原代神经元中，可以通过药理学抑制钙激活蛋白酶（钙蛋白酶）活性或抑制蛋白磷酸酶2B来增加ICP 0蛋白的量（钙调磷酸酶），ICP 0蛋白不能在神经元的细胞核中积累，这表明可能损害病毒在神经元中有效复制的一种机制，并因此有利于在这些细胞中建立病毒潜伏期，可以在IE基因产物的细胞特异性加工中发现。
Infected-cell protein 0 (ICP0), the product of the herpes simplex virus (HSV) immediate-early (IE) alpha 0 gene, is a promiscuous transactivator of viral early (E) and late (L) gene expression. HSV mutants lacking ICP0 function are severely deficient in viral growth and protein synthesis, particularly at low multiplicities of infection. Early in the infectious process in vitro, ICP0 protein accumulates in distinct domains within the nucleus to form characteristic structures active in the transcription of viral genes. However, following infection of primary trigeminal ganglion cells in vitro with a recombinant HSV mutant that expresses only ICP0, we observed that ICP0 protein accumulated in the characteristic intranuclear distribution only in the nuclei of Schwann cells; neurons in the culture did not accumulate ICP0 despite expression of ICP0 RNA in those cells. The same phenomenon was observed in PC12 cells differentiated to assume a neuronal phenotype, In primary neurons in culture, the amount of ICP0 protein could be increased by pharmacologic inhibition of calcium-activated protease (calpain) activity or by inhibition of protein phosphatase 2B (calcineurin), The failure of ICP0 protein to accumulate in the nucleus of neurons suggests that one mechanism which may impair efficient replication of the virus in neurons, and thus favor the establishment of viral latency in those cells, may be found in the cell-specific processing of that IE gene product.