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: 7006060
• 负责人: Thomas C Heineman
• 金额: $ 6.64万
• 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/7006060
• 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（由申请方提供）：水痘-带状疱疹病毒（VZV）是疱疹病毒家族的成员。VZV感染会导致水痘，通常会自行消退。初次感染后，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可以从潜伏期重新激活并重新感染皮肤，导致带状疱疹。急性症状缓解后，相当一部分带状疱疹患者在皮疹部位出现持久的剧烈疼痛，称为带状疱疹后神经痛（PHN）。PHN对药物治疗具有高度抗性，使其成为一种特别使人衰弱的疾病，可持续多年。带状疱疹、PHN和其他由VZV再激活引起的疾病是常见的，并导致大量的发病率。HSV-1和PRV的研究为疱疹病毒感染神经元提供了有价值的见解。然而，VZV再激活引起的独特临床综合征以及其在培养细胞中独特的生长特性强调了在神经元组织中直接研究这种病原体的必要性。到目前为止，还没有研究报告解决VZV组装和神经细胞中的出口的分子生物学。所提出的实验的目标是通过产生荧光标记的VZV重组病毒并评估其感染培养的神经元并表达荧光蛋白的能力来促进此类研究。这些研究的成功完成将导致试剂和技术的开发，为VZV发病机制的分子生物学研究开辟新的途径。