HSV 1 LATENCY--IMMUNIZATION AND RECURRENT OCULAR DISEASE

复发性疱疹性角膜炎是角膜炎的主要原因 今天美国的失明。 目前的长期目标 研究是通过改善视力丧失的发生率， 了解HSV-1潜伏期的基本机制， 再激活和复发性疾病。 第一次提出具体 为了实现这一重要的长期目标， 单纯1型（HSV-1）基因在潜伏期的表达， 重新激活 这些研究将在兔子、小鼠、 和人类病理学标本，使用（1）共培养， 证明感染性病毒，（2）与 特异性基因探针，以证明mRNA转录，和（3） 用单克隆抗体进行免疫组织学检查 翻译特定的蛋白质。 这些研究还将测试 假设HSV-1可以在外周、非- 眼神经节部位、角膜以及中央 三叉神经节 延迟的概念在 一个外围部位也将用于测试一种新的疱疹病毒模型， 基于活性、有限病毒转录的基质性角膜炎， 可能在角膜内平移。 第二个具体目标是 继续研究重新激活的药理学 使用离子电渗法在不同动物种属中潜伏HSV-1 再活化模型 长期目标是找到一种治疗方法 抑制患者中潜伏HSV-1再活化的药剂 有明确的复发病史，因此 防止反复的眼部脱落，复发性疾病， 失明的危险人群。

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.