VARICELLA VIRUS LATENCY

水痘病毒潜伏期

• 批准号: 6346296
• 负责人: RAVI MAHALINGAM
• 金额: $ 24.29万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6346296
• 关键词: Alphaherpesvirinae; Cercopithecidae; ganglion cell; genetic transcription; green fluorescent proteins; latent virus infection; nervous system infection; neurotropic virus; polymerase chain reaction

Clinical, pathological, immunological and virological features of simian varicella virus (SVV) infection in primates are virtually identical to those of varicella zoster virus (VZV) infection in humans. Further, the SVV and VZV genomes are similar in size and structure, show striking homology in their configuration and DNA sequences, and encode antigenically related polypeptides. During latency, both viruses are present in multiple ganglia along the entire neuraxis of their respective hosts, and at least one common gene is transcribed. Finally, unlike any current animal model of varicella latency, both VZV and SVV reactivate from latently infected ganglia of their natural host. These features provide a rationale for our hypothesis that the physical state of latent SVV in monkeys is not similar, if not identical, to VZV in humans. Human ganglia cannot be removed during life, whereas monkey ganglia latently infected with SVV can be readily obtained during life. Thus, we will use in situ PCR and SVV-expressing green fluorescent protein (GFP) to identify the ganglionic cell(s) that harbors latent SVV. Also, based on our accumulating knowledge of the complete nucleotide sequences of the SVV genome, we will determine, during life, the transcriptional pattern of SVV genes in latently infected monkey ganglia. Finally, we will determine if the expression of SVV gene 21 (that is transcribed during latency in monkey ganglia) is required for establishment of latency. A detailed analysis of the physical state of latent simian varicella virus will lead to experiments designed to understand and prevent human varicella reactivation, a cause of serious neurologic disease, particularly in the rapidly increasing elderly and immunocompromised populations.

猴瘟的临床、病理、免疫学和病毒学特征 水痘病毒（SVV）感染灵长类动物几乎相同， 水痘带状疱疹病毒（VZV）感染的人。此夕h SVV和VZV基因组在大小和结构上相似， 它们构型和DNA序列具有同源性，并编码 抗原相关多肽。在潜伏期内，两种病毒都 存在于多个神经节沿着其各自的整个神经轴 宿主，并且至少一个共同基因被转录。最后，不像任何 目前水痘潜伏期的动物模型，VZV和SVV都重新激活 从潜伏感染的神经节中分离出来这些特征 为我们的假设提供了一个理论基础，即潜伏的物理状态 猴子中的SVV与人类中的VZV即使不相同，也不相似。人类 神经节不能在生活中被移除，而猴子的神经节潜伏着 SVV感染者在生活中很容易获得。因此，我们将使用 原位PCR和SVV表达绿色荧光蛋白（GFP）鉴定 潜伏SVV的神经节细胞。此外，根据我们的 积累SVV的完整核苷酸序列的知识 基因组，我们将确定，在生活中，SVV的转录模式， 潜伏感染的猴子神经节中的基因。最后，我们将确定 SVV基因21的表达（在潜伏期期间转录， 猴神经节）是建立潜伏期所必需的。详细 对潜伏的猿水痘病毒的物理状态的分析将导致 旨在了解和预防人类水痘的实验 再激活是严重神经系统疾病的原因，特别是在 快速增加的老年人和免疫功能低下的人群。