OCULAR HERPES--MURINE MODEL

眼疱疹--鼠模型

• 批准号: 3260565
• 负责人: JUDITH A. WHITTUM-HUDSON
• 金额: $ 14.91万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3260565
• 关键词: B lymphocyte; T lymphocyte; antiviral antibody; delayed hypersensitivity; disease /disorder model; enzyme linked immunosorbent assay; genetic strain; helper T lymphocyte; herpes simplex virus 1; histochemistry /cytochemistry; histopathology; immunity; immunosuppression; laboratory mouse; latent virus infection; lymphokines; microorganism immunology; molecular pathology; mutant; necrosis; ocular herpes; radiation immunosuppression; retinitis; steroid biosynthesis; suppressor T lymphocyte; tissue /cell culture; virus antigen; virus cytopathogenic effect

The pathogenesis of ocular disease induced by herpes simplex virus Type 1 is poorly understood, in part because of the inherent difficulty in differentiating between immune- and virus-mediated cytopathic effects occurring at the site of infection. The proposed studies involve continued use of a mouse model of herpetic retinitis induced by unilateral anterior chamber inoculation of HSV-1. Characteristic ocular pathology develops, while virus spread to the opposite eye is associated with contralateral retinal necrosis. Systemic immunity is aberrant because anti-HSV delayed hypersensitivity is actively suppressed while anti-HSV antibody responses are intact. Even so, T cells are absolutely essential for ispilateral retinal preservation. We will attempt to determine (1) how systemic immunity induced by intracameral HSV-1 limits virus spread to protect retinas from disease, (2) how the immune system can be manipulated to prevent the pathogenic sequellae of HSV-1 infection, and (3) the intraocular immune elements which may account for ipsilateral protective events or contralateral exacerbation of retinitis and uveitis. A combination of in vivo and in vitro methods with wildtype KOS strain and drug-induced mutants or recombinant strains will be used to identify retinal protective inducer and/or effector T cell subsets and their mechanisms and site(s) of action which limit virus spread. We will attempt to determine the relationship of these protective subpopulation(s) to systemic suppression of delayed hypersensitivity. Herpetic retinitis caused by a number of herpeviruses can produce clinical problems in immunodeficient or immunologically normal patients. Increased understanding of the role of local and systemic immunity in disease pathogenesis after HSV-1 infection is critical for the development of more effective therapeutic measures in herpetic ocular disease.

单纯疱疹病毒引起的眼部疾病的发病机制 类型 1 人们知之甚少，部分原因是其固有的 难以区分免疫介导和病毒介导的 感染部位发生细胞病变效应。 这 拟议的研究涉及继续使用疱疹小鼠模型 单侧前房接种诱发视网膜炎 HSV-1。 出现特征性眼部病理学，而病毒 扩散到另一只眼睛与对侧视网膜有关 坏死。 由于抗 HSV 延迟，全身免疫异常 抗 HSV 抗体可主动抑制超敏反应 响应完好无损。 即便如此，T细胞仍然是绝对必要的 用于保留同侧视网膜。 我们将尝试确定（1）系统免疫是如何诱导的 前房内 HSV-1 限制病毒传播以保护视网膜 疾病，（2）如何操纵免疫系统来预防 HSV-1 感染的致病性后遗症，以及 (3) 眼内免疫元件可能会导致同侧 保护性事件或对侧视网膜炎恶化以及 葡萄膜炎。 体内和体外方法的结合 野生型KOS菌株和药物诱导的突变体或重组菌株 将用于识别视网膜保护诱导物和/或效应物 T 细胞亚群及其机制和作用位点 限制病毒传播。 我们将尝试确定关系 这些保护性亚群的系统性抑制 迟发性超敏反应。 由多种疱疹病毒引起的疱疹性视网膜炎可产生 免疫缺陷或免疫正常的临床问题 患者。 加深对本地和本地角色的了解 HSV-1感染后疾病发病机制中的全身免疫 对于开发更有效的治疗措施至关重要 在疱疹性眼病中。