OCULAR & OTHER VARICELLA/ZOSTER DISEASE IN MODELS

眼科

• 批准号: 3262952
• 负责人: EDMUND C DUNKEL
• 金额: $ 25.56万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3262952
• 关键词: DNA; RNA; acyclovir; antiviral agents; central nervous system; chickenpox; disease /disorder model; eye disorder chemotherapy; eye infections; ganglions; genetic translation; genome; guinea pigs; histopathology; immunosuppression; laboratory rabbit; latent virus infection; molecular pathology; natural gene amplification; nucleic acid hybridization; nucleic acid probes; ocular herpes; ribosomal proteins; shingles; tissue /cell culture; trigeminal nerve; varicella zoster virus; virus cytopathogenic effect; virus infection mechanism; western blottings

Varicella zoster virus (VZV) is a ubiquitous infectious agent. The natural history pathophysiology, and effective therapy of the clinical diseases are only partially characterized by functional and molecular assays. Varicella is the most common infectious disease in the USA. Reactivated "latent" VZV infection, herpes zoster, is a widespread, often debilitating disease especially in the elderly or immunocompromised patient. Of the estimated 300,000 new cases of zoster annually in this country, nearly 56,000 involve the eye with more than 50-% of patients suffering visual loss as a result of acute or chronic disease. The development of the guinea pig model of ocular VZV infection and analysis by virus recovery, clinical, and molecular biology techniques has allowed for characterization of VZV-induced ocular and systemic disease processes. Long-term objectives of this application are to investigate the presence of VZV DNA and evaluate the activity of the VZV genome (VZV RNA production) in neuronal (trigeminal ganglia) and exraneuronal ((ocular) tissues during acute, latent, and reactivating infection in the guinea pig and rabbit VZV infection models. Specific aims include: (1) detection of VZV DNA and sense and antisense VZV RNA to Immediate Early, Early and other VZV gene areas by hybridization in ocular and CNS tissues, (2) analysis of VZV RNA-induced proteins (ie, role of VZV RNA during latency, and (3) evaluation of currently available and new antiviral agents during acute and reactivating VZV infection. All proposed studies will utilize clinical parameters, VZV recovery assays, and sensitive molecular virology dot/slot, in situ, Northern, and Western blot techniques to characterize the VZV host-cell interactions and VZV-induced translational products during VZV infection stages. In addition, the polymerase chain reaction technique will be used to amplify selectively VZV DNA and VZV RNA in situ and in nucleic acid extraction studies and will allow for investigation of VZV DNA and VZV RNA retained in low copy umber. Knowledge of VZV host-cell interactions will led to more effective therapies to combat the devastating ocular and systemic effects of VZV reactivating infection in both immunocompetent and the increasing population of immunocompromised AIDS, blood dyscrasia, and organ transplant patients.

水痘带状疱疹病毒（VZV）是一种普遍存在的传染剂。 这 自然史病理生理学和临床的有效治疗 疾病仅以功能和分子为特征 测定。水痘是美国最常见的传染病。 重新激活的“潜在” VZV感染，带状疱疹，是一个普遍的 通常会使疾病使人衰弱，尤其是在老年人中或 免疫功能低下的患者。 在估计的300,000个新案例中 每年在这个国家，将近56,000只涉及到超过的眼睛 由于急性或慢性，有50％的患者患有视觉丧失的患者 疾病。 眼VZV感染的豚鼠模型的发展和 通过病毒恢复，临床和分子生物学技术分析 允许表征VZV诱导的眼和全身性 疾病过程。 该应用程序的长期目标是 研究VZV DNA的存在并评估VZV的活性 神经元（三叉神经节）的基因组（VZV RNA产生）和 急性，潜在和重新激活期间（眼部）组织 豚鼠和兔VZV感染模型中的感染。 具体的 目的包括：（1）检测VZV DNA以及感官和反义VZV RNA 通过杂交中的早期，早期和其他VZV基因区域 眼组织和CNS组织，（2）VZV RNA诱导的蛋白（即， VZV RNA在延迟期间的作用，（3）当前评估 急性和重新激活VZV期间可用和新的抗病毒药物 感染。 所有提出的研究将利用临床参数，VZV 恢复测定和敏感的分子病毒点/插槽，原位 北部和蛋白质印迹技术来表征VZV宿主细胞 VZV感染期间的相互作用和VZV诱导的翻译产物 阶段。 另外，聚合酶链反应技术将是 用于在原位和核中选择性扩增VZV DNA和VZV RNA 酸提取研究，将允许研究VZV DNA和 VZV RNA保留在低复制的Umber中。 对VZV主机互动的了解将导致更有效 抗击VZV的毁灭性眼和全身影响的疗法 免疫能力和增加的感染激活 免疫功能低下的艾滋病人群，血液障碍和器官 移植患者。