LATENCY IN HERPESVIRUS INFECTIONS OF CELLS AND TISSUES

细胞和组织的疱疹病毒感染的潜伏期

• 批准号: 3124275
• 负责人: JACK G STEVENS
• 金额: $ 53.67万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-11-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124275
• 关键词: Betaherpesvirinae; Herpes simplex disease; gene expression; genetic manipulation; genetic transcription; genital herpes; herpes simplex virus 1; in situ hybridization; laboratory mouse; laboratory rabbit; laboratory rat; latent virus infection; neurotropic virus; polymerase chain reaction; suid alphaherpesvirus 1; virulence; virus DNA; virus genetics; virus replication

Herpesviruses are ubiquitous and continue to be responsible for significant morbidity and mortality in the human population. In addition, with the increasing incidence of syndromes in which immunosuppression represents a base, there is a corresponding increase in numbers of clinically significant herpesvirus infections. The long-term objective of this proposal is a neurovirulence, and neuroinvasiveness--knowledge that is fundamental to design of methods for control of these agents. Although the primary interest is in Herpes simplex type I (HSV-I), studies presented. With respect to HSV-I, a molecular and functional analysis of the latent phase transcription units facilitate viral reactivation, and a definition of other viral genes functioning in reactivation is also sought. Comparative studies will be concerned with HSV-II and PrV. Investigations of CMV (initially murine, and then human) will focus on identifying latently. Infected cells and defining viral transcription in these cells. These aims will be accomplished in experimental animals (principally mice and rabbits), and will involve the application of contemporary molecular biological approaches coupled with more traditional virologic and experimental pathologic methods. In studies of HSV neuroinvasiveness and latency, animals will be inoculated on rear footpads, and lumbosacral spinal ganglia will be the organs of particular interest. Viral reactivation studies will employ the rabbit cornea-epinephrine model. Cytomegalovirus will be studied principally in murine spleens after parenteral inoculation. When a foundation has been established in the model, investigations of appropriate human autopsy-derived material will follow. Of particular importance with respect to methods will be those concerned with 1) the generation and application of HSV-1 recombinants with various inserts and deletions in the genomic region encoding the latency associated transcription unit, 2) biological analysis of viral genes involved in neuroinvasiveness and neurovirulence, and 3) technologies for development of a more readily investigated "reactivation system" than the rabbit cornea model presently serving as the base for study. In all systems, continued application of in situ hybridization technologies to identify involved cells and viral transcripts will be employed.

疱疹病毒无处不在，并继续对 人类人口的发病率和死亡率。此外，使用 免疫抑制表现为 基础上，临床上有相应的增加。 严重的疱疹病毒感染。这样做的长期目标是 建议是一种神经毒性和神经侵袭性--知识是 设计控制这些制剂的方法的基础。尽管 目前的研究表明，主要研究对象是I型单纯疱疹病毒(HSV-I)。 关于HSV-I，潜伏期的分子和功能分析 阶段转录单位促进病毒重新激活，并定义 也在寻找在重新激活过程中起作用的其他病毒基因。 比较研究将关注HSV-II和PRV。调查 CMV(最初是小鼠，然后是人)将专注于识别 潜伏着。感染细胞并定义这些细胞中的病毒转录。 这些目标将在实验动物(主要是小鼠)身上实现 和兔子)，并将涉及当代分子的应用 生物学方法与更传统的病毒学和 实验病理方法。在单纯疱疹病毒神经侵袭性和 潜伏期，动物将接种在后脚垫和腰椎上 脊神经节将是人们特别感兴趣的器官。病毒式传播 再激活研究将采用兔角膜-肾上腺素模型。 巨细胞病毒将主要在小鼠的脾中进行研究 非肠道接种。当一个基金会在 模型，对适当的人类尸检衍生材料的调查将 跟着。在方法方面特别重要的是那些 1)单纯疱疹病毒1型重组体的产生和应用 编码潜伏期的基因组区域中的各种插入和缺失 相关转录单位，2)病毒基因的生物学分析 涉及神经侵袭性和神经毒性，以及3)用于 开发一种比以前更容易研究的“再激活系统” 目前以兔角膜模型为基础进行研究。总而言之， 系统，继续应用原位杂交技术 识别涉及的细胞和病毒转录本将被使用。