Analysis of pathogenesis of neuronal damage by varicella-zoster virus.

水痘带状疱疹病毒神经元损伤的发病机制分析。

基本信息

批准号：
10670292
负责人：
IWASAKI Takuya
金额：
$ 1.86万
依托单位：
National Institute of Infectious Diseases
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670292/
关键词：
Varicella-zoster virus Herpes zoster Skin Immediate early gene Late gene Demyelination

项目摘要

Reactivation of varicella-zoster virus (VZV) in the dorsal root or trigeminal ganglia causes herpes zoster The pathway of viral spread from the ganglia to the skin and also within the skin is not yet completely understood. Histological studies have revealed that each skin lesion in herpes zoster progresses sequentially through the stages of erythema, vesicles, pustules and finally ulceration. An immunohistochemical study of the early skin lesions of herpes zoster demonstrated a high incidence of hair follicle involvement and the main localization of the virus at the isthmus. This evidence suggests that VZV initially spreads from the ganglia through myelinated nerves, which predominantly end around the isthmus of hair follicles. To further investigate the viral spread within the skin, we analyzed the sequential appearance of the immediate early proteins encoded by ORF 63 of VZV (IE63), using an anti-IE63 antibody raised by rabbit immunization with a GST-fusion protein. This antibody could detect IE63 in a western blot analysis of infected cells and also in immunohistochemical analysis of the skin lesions of herpes zoster. IE63 initially appeared in the nuclei of the follicular epithelial cells and basal or parabasal epidermal cells. Later, the nuclei and cytoplasm of cells in the epidermis and hair follicles became positive. IE63 remained in the virus-infected cells even during their degeneration. When we examined the hair follicles in the early erythematous lesions, cells positive for IE63 were predominantly distributed around the isthmus. In addition, some lymphocytes around the blood vessels were also positive for IE63, but these cells were seldom positive for the structural antigen. Thus, these observations suggest that VZV arriving through myelinated nerves infects not only permissive cells, but also non-permissive cells in the involved skin of herpes zoster.

背根或三叉神经节中的水痘带状疱疹病毒 (VZV) 重新激活会导致带状疱疹。病毒从神经节传播到皮肤以及皮肤内的途径尚不完全清楚。组织学研究表明，带状疱疹的每个皮肤病变都依次经历红斑、水疱、脓疱和最终溃疡的阶段。对带状疱疹早期皮肤病变的免疫组织化学研究表明，毛囊受累的发生率很高，并且病毒主要定位于峡部。这一证据表明，水痘带状疱疹病毒最初从神经节通过有髓神经传播，有髓神经主要终止于毛囊峡部周围。为了进一步研究病毒在皮肤内的传播，我们使用 GST 融合蛋白免疫兔子产生的抗 IE63 抗体，分析了 VZV 的 ORF 63 (IE63) 编码的立即早期蛋白的顺序出现。该抗体可以在感染细胞的蛋白质印迹分析以及带状疱疹皮损的免疫组织化学分析中检测 IE63。 IE63最初出现在滤泡上皮细胞和基底或副基底表皮细胞的细胞核中。随后，表皮和毛囊细胞核和细胞质呈阳性。即使在病毒感染的细胞退化期间，IE63 仍保留在病毒感染的细胞中。当我们检查早期红斑病变的毛囊时，IE63 阳性细胞主要分布在峡部周围。此外，血管周围的一些淋巴细胞也呈IE63阳性，但这些细胞很少呈结构抗原阳性。因此，这些观察结果表明，通过有髓神经到达的 VZV 不仅感染带状疱疹相关皮肤中的允许细胞，而且还感染非允许细胞。