HSV 1 LATENCY--IMMUNIZATION AND RECURRENT OCULAR DISEASE

复发的疱疹病毒性角膜炎是导致角膜病变的主要原因 当今美国的盲人。当前的长期目标 一项研究是通过改善视力降低视力损失的发生率 了解HSV-1潜伏的基本机制， 重新激活，和复发的疾病。第一个提出的具体建议 目的是为了满足这一重要的长期目标，即研究疱疹 单纯疱疹病毒1型(HSV-1)在潜伏期和 重新激活。这些研究将在兔子、小鼠、 和人类病理标本使用(1)共培养以 演示传染性病毒，(2)与 特异的基因探针，以显示mRNA转录，以及(3) 用单抗免疫组化学方法证明 特定蛋白质的翻译。这些研究还将测试 假设HSV-1可以在外周建立潜伏期， 神经节细胞眼部，角膜，以及中央 神经节部位，三叉神经节。延迟的概念在 一个外围站点也将用于测试一种新的疱疹模型 基于活跃的、有限的病毒转录和 可能是角膜内的平移。第二个具体目标是 继续研究其复活的药理作用 离子导入法检测不同动物体内潜伏的HSV-1 重新激活模型。长期目标是找到一种治疗方法 将抑制患者潜伏的HSV-1重新激活的药物 有复发性疾病的既定病史，因此 防止反复眼球脱落，复发疾病，并可能 处于失明危险中的人群。

Recurrent herpetic keratitis is the leading cause of corneal blindness in the U.S. today. The long term goal of the present study is reduce the incidence of visual loss through an improved understanding of the basic mechanisms of HSV-1 latency, reactivation, and recurrent disease. The first proposed specific aim to meet this important long term objective is to study herpes simplex type 1 (HSV-1) gene expression during latency and reactivation. These studies will be carried out in rabbits, mice, and human pathological specimens using (1) cocultivation to demonstrate infectious virus, (2) in situ hybridization with specific gene probes to demonstrate mRNA transcription, and (3) immunohistology with monoclonal antibodies to demonstrate translation of specific proteins. These studies will also test the hypothesis that HSV-1 can establish latency at a peripheral, non- ganglionic ocular site, the cornea, as well as at a central ganglionic site, the trigeminal ganglia. The concept of latency at a peripheral site will also be used to test a new model of herpetic stromal keratitis based on active, limited viral transcription and possible translation within the cornea. The second specific aim is to continue the study of the pharmacology of reactivation of latent HSV-1 in different animal species using the iontophoresis reactivation model. The long term goal is to find a therapeutic agent that will inhibit reactivation of latent HSV-1 in patients with an established history of recurrent disease, and thereby prevent repeated ocular shedding, recurrent disease, and possible blindness in the population at risk.