Chen X p, Li J, Mata M, Goss J, Wolfe D, Glorioso J C, Fink D J
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
J Virol. 2000 Nov;74(21):10132-41. doi: 10.1128/jvi.74.21.10132-10141.2000.
Infected-cell protein 0 (ICP0), the product of the herpes simplex virus (HSV) immediate-early (IE) alpha0 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.
感染细胞蛋白0（ICP0）是单纯疱疹病毒（HSV）立即早期（IE）α0基因的产物，是病毒早期（E）和晚期（L）基因表达的一种多效性反式激活因子。缺乏ICP0功能的HSV突变体在病毒生长和蛋白质合成方面严重缺陷，尤其是在低感染复数时。在体外感染过程早期，ICP0蛋白在细胞核内的不同区域积累，形成对病毒基因转录有活性的特征性结构。然而，在用仅表达ICP0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ICP0蛋白仅在施万细胞的细胞核中以特征性的核内分布积累；培养物中的神经元尽管在这些细胞中表达了ICP0 RNA，但并未积累ICP0。在分化为神经元表型的PC12细胞中也观察到了同样的现象。在培养的原代神经元中，ICP0蛋白的量可以通过钙激活蛋白酶（钙蛋白酶）活性的药理抑制或蛋白磷酸酶2B（钙调磷酸酶）的抑制来增加。ICP0蛋白未能在神经元细胞核中积累表明，在该IE基因产物的细胞特异性加工过程中，可能存在一种机制会损害病毒在神经元中的有效复制，从而有利于病毒在这些细胞中建立潜伏状态。
