Iwasaki T, Muraki R, Kasahara T, Sato Y, Sata T, Kurata T
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Arch Virol Suppl. 2001(17):109-19. doi: 10.1007/978-3-7091-6259-0_12.
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 immunization of rabbits with a recombinant 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.
水痘带状疱疹病毒（VZV）在背根神经节或三叉神经节中重新激活会引发带状疱疹。病毒从神经节传播至皮肤以及在皮肤内的传播途径尚未完全明确。组织学研究表明，带状疱疹的每个皮肤损害依次经历红斑、水疱、脓疱，最终溃疡阶段。一项对带状疱疹早期皮肤损害的免疫组织化学研究显示，毛囊受累的发生率很高，且病毒主要定位于峡部。这一证据表明，VZV最初通过有髓神经从神经节传播，这些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，我们使用通过用重组蛋白免疫兔子产生的抗IE63抗体，分析了VZV的ORF 63编码即刻早期蛋白（IE63）的相继出现情况。该抗体在感染细胞的蛋白质印迹分析以及带状疱疹皮肤损害的免疫组织化学分析中均能检测到IE63。IE63最初出现在滤泡上皮细胞以及基底或基底旁表皮细胞的细胞核中。随后，表皮和毛囊中细胞的细胞核及细胞质均呈阳性。即使在病毒感染的细胞发生变性时，IE63仍保留在这些细胞中。当我们检查早期红斑性损害中的毛囊时，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IE63也呈阳性，但这些细胞很少对结构抗原呈阳性。因此，这些观察结果表明，通过有髓神经到达的VZV不仅感染允许性细胞，还感染带状疱疹受累皮肤中的非允许性细胞。
