EGFP-Tagged VZV for the Study of Neuronal Infection

EGFP 标记的 VZV 用于神经元感染研究

• 批准号: 6858199
• 负责人: Thomas C Heineman
• 金额: $ 6.8万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-15 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858199
• 关键词: confocal scanning microscopy; green fluorescent proteins; human tissue; immunocytochemistry; latent virus infection; molecular biology; nervous system infection; neurons; plasmids; reagent /indicator; recombinant virus; shingles; site directed mutagenesis; technology /technique development; tissue /cell culture; varicella zoster virus; virus assembly; virus cytopathogenic effect; virus infection mechanism

DESCRIPTION (provided by applicant): Varicella-zoster virus (VZV) is a member of the herpesvirus family. Infection with VZV causes chickenpox, which typically resolves on its own. Following primary infection, VZV establishes lifelong latency in neurons within the dorsal root ganglia of the host. Later in life, VZV can reactivate from latency and re-infect the skin to cause shingles. After resolution of the acute symptoms, a substantial proportion of shingles patients develop long-lasting, severe pain at the site of the rash referred to postherpetic neuralgia (PHN). PHN is highly resistant to medical therapy making it a particularly debilitating illness that can persist for years. Shingles, PHN and other diseases resulting from VZV reactivation are common and cause substantial morbidity. Valuable insights into herpesvirus infection of neurons have been provided by studies of HSV-1 and PRV. However, the unique clinical syndromes caused by VZV reactivation as well as its distinctive growth properties in cultured cells emphasize the need for direct studies of this pathogen in neuronal tissue. To date no studies have been reported addressing the molecular biology of VZV assembly and egress in nerve cells. The goal of the proposed experiments is to facilitate such studies by generating fluorescent tagged VZV recombinant viruses and assessing their ability to infect and express the fluorescent proteins in cultured neurons. Successful completion of these studies will result in reagents and the development of techniques that will open new avenues of research into the molecular biology of VZV pathogenesis.

描述（由申请人提供）：水痘带状疱疹病毒（VZV）是疱疹病毒家族的一员。感染VZV会导致水痘，而水痘通常会自行消退。原发感染后，VZV在宿主背根神经节内的神经元中建立终身潜伏期。在以后的生活中，VZV可以从潜伏中重新激活并重新感染皮肤导致带状疱疹。急性症状消退后，相当大比例的带状疱疹患者在皮疹部位出现持久、剧烈的疼痛，称为带状疱疹后神经痛（PHN）。PHN对药物治疗有很强的抵抗力，使其成为一种特别虚弱的疾病，可以持续多年。带状疱疹，PHN和其他由VZV再激活引起的疾病是常见的，并导致大量发病率。通过对HSV-1和PRV的研究，对疱疹病毒感染神经元提供了有价值的见解。然而，由VZV再激活引起的独特临床综合征及其在培养细胞中的独特生长特性强调了对该病原体在神经组织中的直接研究的必要性。到目前为止，还没有关于VZV在神经细胞中组装和输出的分子生物学研究报道。本实验的目的是通过生成荧光标记的VZV重组病毒，并评估其在培养的神经元中感染和表达荧光蛋白的能力，从而促进这类研究。这些研究的成功完成将导致试剂和技术的发展，这将为研究VZV发病机制的分子生物学开辟新的途径。