OCULAR HSV--LATENCY, REACTIVATION, AND RECURRENCE

眼部单纯疱疹病毒——潜伏期、再激活和复发

• 批准号: 2019527
• 负责人: JAMES M HILL
• 金额: $ 19.7万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019527
• 关键词: DNA methylation; Saimiri; disease /disorder model; epinephrine; ganglions; gene expression; genetic promoter element; herpes simplex virus 1; hyperthermia; immediate early protein; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rabbit; latent virus infection; nontherapeutic iontophoresis; ocular herpes; polymerase chain reaction; relapse /recurrence; virus DNA; virus RNA; virus cytopathogenic effect; virus genetics

The PI proposes to elucidate the pharmacological and molecular mechanisms that underlie reactivation of latent HSV from trigeminal ganglia (TG). A variety of studies involving HSV DNA and the RNAs designated as latency-associated transcripts (LAT) will be done using animal models of HSV reactivation. The specific aims are 1) to determine the relationship between specific sequence elements in the LAT promoter and the mechanisms that govern the ability to undergo in vivo adrenergic reactivation; 2) to detect and quantitate HSV transcripts in he TG from animals harboring latent viruses that exhibit different phenotypes and genotypes before and after adrenergic reactivation; and 3) to characterize the pharmacological and molecular mechanisms involved in propranolol inhibition of in vivo reactivation in animals harboring latent viruses that exhibit different phenotypes and genotypes. The methodology includes iontophoresis of epinephrine and hyperthermia to induce HSV reactivation, slit-lamp examination to detect spontaneous corneal epithelial lesions, sequence analysis of LAT regions of HSV DNA, detection of HSV DNA methylation, and RT- PCR to quantitate HSV RNAs. The long-term goal is to provide insights into HSV pathogenesis that could result in the development of therapeutic strategies to block neuronal HSV reactivation and the morbidity caused by repeated episodes of herpetic disease.

PI提议阐明药理和分子 三叉神经的潜在HSV重新激活的机制 神经节（TG）。 涉及HSV DNA和RNA的各种研究 指定为与延迟相关的成绩单（LAT）的指定 HSV重新激活的动物模型。 具体目的是1）确定特定之间的关系 LAT启动子中的序列元素和机制 控制体内肾上腺素能重新激活的能力； 2）到 从动物中检测并定量HSV转录本 具有表现出不同表型的潜在病毒和 肾上腺素能重新激活之前和之后的基因型；和3）到 表征涉及的药理和分子机制 在抑制携带动物体内重新激活的普萘洛尔 表现出不同表型和基因型的潜在病毒。 方法包括肾上腺素和高温的离子噬菌体 为了诱导HSV重新激活，请检查扫描灯检查以检测 自发角膜上皮病变，LAT的序列分析 HSV DNA的区域，HSV DNA甲基化的检测和RT- PCR定量HSV RNA。 长期目标是提供 对HSV发病机理的见解，这可能导致 阻止神经元HSV重新激活的治疗策略和 由疱疹性疾病反复发作引起的发病率。