VIRUS INFECTIONS IN THE EYE

我们对各种病毒学和免疫病理学过程的研究， 当病毒在眼部微环境中复制时， 领域：（1）眼部和视神经细胞中的冠状病毒感染，（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 和人类巨细胞病毒（CMV）感染的发病机制。我们有 确定鼠冠状病毒可诱导眼部疾病， 用作研究视网膜变性疾病的模型系统。 这 模型有许多独特的功能。 这种病毒能够诱导 急性感染时存在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， 进行性视网膜退化，甚至在病毒消失几个月后。 病毒主要在Muller细胞中复制，也可以在 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，有遗传和免疫成分， 这种疾病。 视网膜变性的病理表现 疾病可能受到宿主遗传学的影响，即某些菌株 的小鼠对病毒诱导的视网膜退行性变化具有抗性。 的 病理变化也密切相关的发展， 抗视网膜和抗RPE抗体。 这些发现表明， 自身免疫在发病机制中的作用 这种疾病可能被认为是一种模式 用于色素上皮和光感受器的变性疾病 在人类身上。 需要有效的药物治疗和预防疱疹病毒， 其他病毒性疾病也变得越来越重要。 我们发现 leukoregulin是一种天然存在的免疫细胞因子，不仅 增加了药物阿昔洛韦的抗病毒作用， 抑制单纯疱疹病毒的复制，这表明， 免疫疗法和化学疗法可以产生对 疱疹病毒复制，并提供了应用此 治疗病毒感染的方法。 去年开始的研究表明，CMV能够 在体外人RPE细胞内复制;然而，复制是 限制在立即早期蛋白质产生的水平。 低 RPE细胞中立即早期病毒蛋白的表达频率 随后CMV的缓慢复制可能是 它们与病毒持续存在和激活的关系， 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.