Perera L P, Mosca J D, Sadeghi-Zadeh M, Ruyechan W T, Hay J
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Virology. 1992 Nov;191(1):346-54. doi: 10.1016/0042-6822(92)90197-w.
Varicella-Zoster virus (VZV) is a neurotropic alphaherpes virus closely related to herpes simplex virus (HSV). However, unlike its close relative HSV, VZV lacks a functional alpha-TIF (alpha-gene transinducing factor) that activates the transcription of immediate early genes during the initial events of the virus life cycle. Hence, in the absence of a functional alpha-TIF, the mechanism triggering the expression of immediate early genes in VZV at present remains unclear. Accumulating evidence indicates that the gene product of the putative immediate early gene ORF62 (IE62) plays a pivotal role in activating VZV genes of all three putative kinetic classes, namely immediate early (alpha), early (beta), and late (gamma) classes of VZV genes. In the present study, we show that IE62 can positively autoregulate its cognate promoter using a transient transfection assay, both in lymphocytes and in neural cells. In the same system, we can also demonstrate activation of the VZV IE62 promoter by HSV ICP4. By deletion analysis and oligonucleotide-directed site-specific mutagenesis we have localized specific regions in the IE62 promoter/upstream sequences that mediate inducibility by IE62 and HSV ICP4, and provide evidence that this promoter activation by these two proteins may be through different mechanisms. These data, taken together with the recent demonstration of the presence of IE62 in the VZ virion tegument (Kinchington, P.R., Hoagland, J.K., Arvin, A.M., Ruyechan, W.T., and Hay, J. 1992. J. Virol. 66, 359-366) provides a possible mechanism by which the triggering of VZV gene expression occurs in the absence of a functional alpha-TIF protein.
水痘带状疱疹病毒（VZV）是一种嗜神经的α疱疹病毒，与单纯疱疹病毒（HSV）密切相关。然而，与其近亲HSV不同的是，VZV缺乏功能性的α-TIF（α基因反式诱导因子），该因子在病毒生命周期的初始阶段激活立即早期基因的转录。因此，在缺乏功能性α-TIF的情况下，目前触发VZV立即早期基因表达的机制仍不清楚。越来越多的证据表明，推定的立即早期基因ORF62（IE62）的基因产物在激活VZV所有三个推定动力学类别的基因中起关键作用，即VZV基因的立即早期（α）、早期（β）和晚期（γ）类别。在本研究中，我们表明，通过瞬时转染试验，IE62在淋巴细胞和神经细胞中均可正向自调节其同源启动子。在同一系统中，我们还可以证明HSV ICP4对VZV IE62启动子的激活作用。通过缺失分析和寡核苷酸定向位点特异性诱变，我们在IE62启动子/上游序列中定位了介导IE62和HSV ICP4诱导性的特定区域，并提供证据表明这两种蛋白质对该启动子的激活可能通过不同机制。这些数据，连同最近在VZ病毒体被膜中发现IE62的证据（Kinchington，P.R.，Hoagland，J.K.，Arvin，A.M.，Ruyechan，W.T.，和Hay，J. 1992. J. Virol. 66，359 - 366），提供了一种在缺乏功能性α-TIF蛋白的情况下VZV基因表达触发的可能机制。
