VIRUS INFECTIONS IN THE EYE

我们对各种病毒学和免疫病理过程的研究 当病毒在眼部微环境中复制时发生 领域：(1)眼和视神经细胞的冠状病毒感染，(2) 病毒在人类疾病中的可能作用，(3)抗病毒 细胞因子和药物的治疗作用；(4)分子诊断 以及人类巨细胞病毒(CMV)感染的发病机制。我们有 证实小鼠冠状病毒可以诱发眼部疾病，并可能是 作为研究视网膜退行性疾病的模型系统。这 模型有许多独特的功能。该病毒能够诱导一种 急性感染时伴有轻度视网膜血管炎症。 最初的视网膜损伤之后是病毒的清除和 进行性视网膜变性，甚至在病毒消失几个月后。 该病毒主要在穆勒细胞中复制，也可以 在视网膜色素上皮(RPE)和感光细胞中检测到。 最近的研究表明，有遗传和免疫学成分可以 这种病。视网膜退行性变的病理表现 疾病可能会受到宿主的遗传因素的影响，即某些菌株 的小鼠对病毒诱导的视网膜变性改变具有抵抗力。这个 病理改变也与血管病变的发生密切相关。 抗视网膜抗体和抗RPE抗体。这些发现表明， 自身免疫在发病机制中的作用。这种病可以被认为是一种典型的 治疗色素上皮和光感受器退行性疾病 在人类身上。 需要有效的药物治疗和预防疱疹病毒和 其他病毒性疾病也变得越来越重要。我们发现 白细胞调节蛋白，一种自然产生的免疫细胞因子，不仅 增加药物阿昔洛韦的抗病毒作用，也可以直接 抑制单纯疱疹病毒复制，证明了这种结合 免疫疗法和化疗可以产生实质性的抑制 疱疹病毒复制，并提供了应用这一点的理论基础 治疗病毒感染的方法。 过去一年开始的研究表明，CMV能够 在体外的人RPE细胞内复制；然而，复制是 限制在直接早期蛋白质生产的水平。低谷 即刻早期病毒蛋白在RPE细胞中的表达频率 而随后CMV的缓慢复制可能是 它们与病毒持续存在和激活之间的关系 视网膜。

Our studies of various virologic and immunopathologic processes that occur when viruses replicate in the ocular microenvironment comprise four areas: (1) coronavirus infection in ocular and optic nerve cells, (2) the possible roles of viruses in human diseases, (3) antiviral therapeutic actions of cytokines and drugs, and (4) molecular diagnosis and pathogenesis of cytomegalovirus (CMV) infections in man. We have established that murine coronavirus can induce ocular disease and may be used as a model system for studying retinal degenerative diseases. This model has many unique features. The virus is capable of inducing an acute infection in the presence of mild retinal vascular inflammation. Initial retinal damage is followed by clearance of the virus and progressive retinal degeneration, even months after the virus is gone. The virus replicates predominantly in Muller cells and also can be detected in retinal pigment epithelium (RPE) and photoreceptor cells. Recent studies show that there are genetic and immunologic components to this disease. The retinal degenerative pathologic manifestations of the disease can be influenced by the genetics of the host, ie, some strains of mice are resistant to virus-induced retinal degenerative changes. The pathologic changes also are closely related to the development of antiretinal and anti-RPE antibodies. These findings suggest a role for autoimmunity in the pathogenesis. This disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in humans. The need for effective drug treatment and prevention of herpes virus and other viral diseases has assumed growing importance. We found that leukoregulin, a naturally occurring immunologic cytokine, not only increases the antiviral actions of the drug acyclovir but also directly inhibits herpes simplex virus replication, demonstrating that combination immunotherapy and chemotherapy can produce substantial inhibition of herpes virus replication and providing a rationale for applying this approach to treating virus infections. Studies initiated this past year indicate that CMV is capable of replicating within human RPE cells in vitro; however, replication is limited at the level of immediate early protein production. The low frequency of expression of immediate early viral proteins in RPE cells and the subsequent slow replication of CMV may be critical variables in terms of their relationship to viral persistence and activation within the retina.