OCULAR HSV--LATENCY, REACTIVATION, AND RECURRENCE

眼部单纯疱疹病毒——潜伏期、再激活和复发

基本信息

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
项目类别：
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

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

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项目摘要

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。这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。