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

水痘-带状疱疹病毒(VZV)在背根或三叉神经节重新激活会引起带状疱疹，病毒从神经节传播到皮肤和皮肤内的途径尚不完全清楚。组织学研究表明，带状疱疹的每一种皮肤损害都会依次经历红斑、水泡、脓疱和最终溃烂阶段。对带状疱疹早期皮肤损害的免疫组织化学研究表明，毛囊受累的发生率很高，病毒主要分布在峡部。这一证据表明，VZV最初通过有髓神经从神经节传播，主要结束于毛囊峡部。为了进一步研究病毒在皮肤内的传播，我们用GST融合蛋白免疫兔所产生的抗IE63抗体，分析了VZV ORF 63(IE63)编码的即刻早期蛋白的顺序出现。该抗体可在免疫印迹分析感染细胞和带状疱疹皮肤病变的免疫组织化学分析中检测到IE63。IE63最初出现在滤泡上皮细胞和基底层或基底部表皮细胞的胞核中。后来，表皮和毛囊中的细胞核和细胞质呈阳性。IE63在病毒感染的细胞中即使在退化过程中也仍然存在。当我们检查早期红斑性病变的毛囊时，IE63阳性的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性抗原阳性。因此，这些观察结果表明，通过有髓神经到达的VZV不仅感染带状疱疹受累皮肤中的允许细胞，也感染非允许细胞。

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.