Kennedy P G, Major E O, Williams R K, Straus S E
Medical Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Virology. 1994 Dec;205(2):558-62. doi: 10.1006/viro.1994.1679.
The effects of the varicella-zoster virus (VZV) OKA vaccine strain in producing morphologic and antigenic changes in dissociated cultures of human fetal brain was investigated. Cultures containing 80% glial acidic fibrillary protein (GFAP), GFAP+ (positive) astrocytes and 20% GFAP- (negative) fibroblastic-like cells were infected with cell-free VZV OKA at a multiplicity of infection of 0.1 plaque-forming units per cell. Cytopathic effects and significant viral antigen labeling with antibodies against VZV gpl and immediate-early (IE) protein 62 were first detected 6 to 7 days postinfection. Several observations indicated that astrocyte GFAP expression was altered and diminished as a result of VZV infection itself, thereby raising doubts about the utility of combining cell markers and viral antigenic labeling in assessing the susceptibility of neural cell types to viral infection. The down-regulation of GFAP expression by VZV appears to be mediated by early rather than late events in the viral replication cycle and may not be the result of virally induced global shut-off of host cell protein synthesis. Similar observations were made using VZV Ellen, a multipassaged, nonvaccine strain. These observations have potential in vivo implications related to histologic analysis of VZV-infected tissues and disease pathogenesis.
研究了水痘-带状疱疹病毒(VZV)OKA疫苗株在人胎脑解离培养物中产生形态学和抗原性变化的作用。含有80%胶质酸性纤维蛋白(GFAP)、GFAP+(阳性)星形胶质细胞和20%GFAP-(阴性)成纤维样细胞的培养物,以每细胞0.1个蚀斑形成单位的感染复数,用无细胞VZV OKA进行感染。感染后6至7天首次检测到细胞病变效应以及针对VZV糖蛋白1和即刻早期(IE)蛋白62的抗体对病毒抗原的显著标记。多项观察结果表明,由于VZV感染本身,星形胶质细胞GFAP表达发生改变并减少,从而使人对在评估神经细胞类型对病毒感染的易感性时结合细胞标志物和病毒抗原标记的实用性产生怀疑。VZV对GFAP表达的下调似乎是由病毒复制周期中的早期而非晚期事件介导的,可能不是病毒诱导宿主细胞蛋白质合成全面关闭的结果。使用多传代的非疫苗株VZV Ellen也得到了类似的观察结果。这些观察结果对于VZV感染组织的组织学分析和疾病发病机制具有潜在的体内意义。