DiLoreto D, Epstein L G, Lazar E S, Britt W J, del Cerro M
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, New York.
Lab Invest. 1994 Jul;71(1):141-8.
Cytomegalovirus (CMV) retinitis is a common, devastating complication of AIDS. Strict host specificity of human CMV (HCMV), has limited the study of the virus. The purpose of this research was to create a model that allowed the in vivo infection of human retinal tissue with HCMV.
Small fragments of 13-week human fetal retina were transplanted into the anterior chambers of immune-deficient mice. One week later, 15 of 30 grafts were inoculated with HCMV. Infected and noninfected specimens were compared for histopathologic changes at 14, 30, and 60 days at light and electron microscopic levels. Histochemistry was performed to characterize: level of graft differentiation, range of viral replication cycle, and effects on neuronal, glial, and monocytic elements of the retina.
At 30 and 60 days, grafts were well differentiated histologically and histochemically. The infected grafts showed numerous large cells containing intranuclear and intracytoplasmic inclusions. Ultrastructural examination revealed viral particles within cytoplasm and nuclei. Infected cells expressed proteins representative of all phases of the HCMV replication cycle. Most HCMV-infected cells expressed the neuronal marker, protein gene product 9.5. In a second series of experiments, tissue from one graft harvested at 45 days postinfection was used to recover HCMV in fibroblast cultures and also used successfully to passage the virus to two control grafts.
This model allows HCMV to actively infect and replicate within highly differentiated human neural tissue. It produces pathology characteristic of CMV-infected neural tissue in a time course suitable for long-term study. The nature of this model will allow the study of: the replication properties of HCMV in nervous tissue, the specific effects of HCMV on the human retina, the interaction of HCMV with other viruses, e.g., HIV, and various anti-viral therapies.
巨细胞病毒（CMV）视网膜炎是艾滋病常见的、具有破坏性的并发症。人巨细胞病毒（HCMV）严格的宿主特异性限制了对该病毒的研究。本研究的目的是创建一个能使HCMV在人视网膜组织中进行体内感染的模型。
将13周龄人胎儿视网膜的小片段移植到免疫缺陷小鼠的前房。一周后，30个移植物中的15个接种HCMV。在第14、30和60天，对感染和未感染的标本进行光镜和电镜水平的组织病理学变化比较。进行组织化学以表征：移植物分化水平、病毒复制周期范围以及对视网膜神经元、神经胶质和单核细胞成分的影响。
在第30和60天，移植物在组织学和组织化学上分化良好。感染的移植物显示出许多含有核内和胞质内包涵体的大细胞。超微结构检查显示细胞质和细胞核内有病毒颗粒。感染细胞表达代表HCMV复制周期所有阶段的蛋白质。大多数HCMV感染细胞表达神经元标志物蛋白基因产物9.5。在第二系列实验中，感染后45天收获的一个移植物的组织用于在成纤维细胞培养物中回收HCMV，并且还成功地将病毒传给了两个对照移植物。
该模型使HCMV能够在高度分化的人神经组织中主动感染和复制。它在适合长期研究的时间进程中产生CMV感染神经组织的病理学特征。该模型的性质将有助于研究：HCMV在神经组织中的复制特性、HCMV对人视网膜的具体影响、HCMV与其他病毒（如HIV）的相互作用以及各种抗病毒疗法。
