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: 2057777
• 负责人: JACK G STEVENS
• 金额: $ 54.37万
• 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 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057777
• 关键词: Betaherpesvirinae; Herpes simplex disease; cytomegalovirus; gene expression; genetic manipulation; genetic transcription; genital herpes; herpes simplex virus 1; host organism interaction; 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，并继续造成重大后果 人口的发病率和死亡率。 此外，随着 以免疫抑制为代表的综合征的发生率不断增加 基础上，临床数量也相应增加 明显的疱疹病毒感染。 本次活动的长远目标 提案是一种神经毒力和神经侵入性——知识 是设计控制这些物质的方法的基础。 虽然 研究表明，主要关注的是 I 型单纯疱疹病毒 (HSV-I)。 对于 HSV-I，潜伏病毒的分子和功能分析 相转录单位促进病毒再激活，以及定义 还寻找在重新激活中起作用的其他病毒基因。 比较研究将涉及 HSV-II 和 PrV。 调查 CMV（最初是小鼠，然后是人类）将重点识别 潜伏地。 受感染的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）中实现 和兔子），并将涉及当代分子生物学的应用 生物学方法加上更传统的病毒学和 实验病理方法。 在 HSV 神经侵袭性研究中 潜伏期，动物将在后足垫和腰骶部接种 脊神经节将是特别令人感兴趣的器官。 病毒性的 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脾脏中进行研究 肠外接种。 当基础已经建立在 模型，对适当的人体尸检材料的研究将 跟随。 就方法而言，特别重要的是那些 涉及1）HSV-1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删除 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力，以及3）技术 开发比现有系统更容易研究的“重新激活系统” 兔角膜模型目前作为研究基础。 总共 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。