The synthesis and immunogenicity of varicella-zoster virus glycoprotein E and immediate-early protein (IE62) expressed in recombinant herpes simplex virus-1.
The synthesis and immunogenicity of varicella-zoster virus glycoprotein E and immediate-early protein (IE62) expressed in recombinant herpes simplex virus-1.
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重组单纯疱疹病毒1中表达的水痘带状疱疹病毒糖蛋白E和立即早期蛋白（IE62）的合成和免疫原性。
DOI：
10.1016/s0166-3542(96)01014-5
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发表时间：
1997
影响因子：
7.6
通讯作者：
Arvin,AM
中科院分区：
文献类型：
--
作者：
Lowry,PW;Koropchak,CM;Choi,CY;Mocarski,ES;Kern,ER;Kinchington,PR;Arvin,AM
为了评价水痘带状疱疹病毒（VZV）蛋白在单纯疱疹病毒-1（HSV-1）载体中的最佳表达条件和免疫原性，我们选择了由ORF 68编码的VZV糖蛋白E（gE）和由ORF 62编码的VZV产物，即早期主要被膜蛋白（IE62）。将VZV gE蛋白编码序列沿着启动子插入HSV-1株科斯的胸苷激酶（TK）基因中，将HSV-1 ICP 4启动子表达的VZV gE基因插入HSV-1株F的糖蛋白C（gC）基因中，并将其克隆到HSV-1株F中。（3）将HSV-1 ICP 4启动子控制下的VZV IE62蛋白编码序列插入HSV-1 F株gC基因中。感染细胞单层的免疫印迹分析和免疫过氧化物酶染色证明VZV蛋白的载体表达。在小鼠颅内接种后，VZV gE-HSV（TK）和VZV IE62-HSV（gC）均诱导针对VZV gE或VZV IE62的IgG应答。当使用来自VZV免疫人供体的T淋巴细胞进行细胞毒性试验时，识别VZV gE或VZV IE 62的T淋巴细胞的前体频率范围是相似的，无论这些蛋白质是由HSV-1还是牛痘载体表达。这些实验证明HSV-1是表达这些VZV蛋白的合适载体，并支持针对这些密切相关的α-疱疹病毒设计组合疫苗的可行性。
In order to evaluate the conditions for optimal expression and immunogenicity of varicella-zoster virus (VZV) proteins in a herpes simplex virus-1 (HSV-1) vector, we selected the VZV glycoprotein E (gE), encoded by ORF 68 and the VZV product of ORF 62, an immediate-early major tegument protein (IE62). Three HSV/VZV recombinants were generated: (1) VZV gE protein coding sequences along with the promoter region were inserted into the thymidine kinase (TK) gene of HSV-1 strain KOS; (2) VZV gE expressed from the HSV-1 ICP4 promoter was inserted into the glycoprotein C (gC) gene of HSV-1 strain F; and (3) VZV IE62 protein coding sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC gene of HSV-1 strain F. Immunoblot analysis and immunoperoxidase staining of infected cell monolayers demonstrated vector expression of VZV proteins. Following intracranial inoculation in mice, both VZV gE-HSV (TK) and VZV IE62-HSV (gC) induced an IgG response against VZV gE or VZV IE62. When tested in cytotoxicity assays using T-lymphocytes from VZV immune human donors, the range of precursor frequencies for T-lymphocytes that recognized VZV gE or VZV IE62 was similar whether these proteins were expressed by HSV-1 or a vaccinia vector. These experiments demonstrate that HSV-1 is a competent vector for expression of these VZV proteins and support the feasibility of engineering a combined vaccine for these closely related α-herpesviruses.