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HSV-1 GENE EXPRESSION IN LATENCY INFECTED NEURONS

潜伏期感染神经元中的 HSV-1 基因表达

基本信息

批准号：
6169973
负责人：
LAWRENCE T FELDMAN
金额：
$ 25.17万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 2002-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6169973
关键词：
Herpes simplex disease RNA splicing RNase protection assay gene expression gene induction /repression genetic mapping genetic promoter element genetic transcription herpes simplex virus 1 laboratory mouse latent virus infection molecular cloning neurons recombinant virus tissue /cell culture virus replication

项目摘要

DESCRIPTION (Adapted from Applicant's Abstract): Recurrences of herpes simplex virus infections afflict millions of Americans. Recurrent infections also serve as an important source of communicable virus. Clinical disease is especially important in the immunocompromised patients and in recurrences during childbirth. The applicant proposes to use a mouse foot pad model to study significant molecular events in the establishment, maintenance and reactivation phases of the herpes simplex virus cycle. The in vivo studies focus on the LAT cap region and LAT promoter, which is the only promoter active in latent infection. These studies include the specific mechanism for neuronal specific transcription in mouse neural tissues as well as the mechanism responsible for keeping the LAT promoter active during latency when all other promoters are shut off. Studies on the LAT intron will further document the molecular nature of this RNA including additional proofs that it is an intron by mutation of the splicing signals. Other experiments may provide some insight into why it is so stable. A fundamental switch in the virus life cycle between productive and latent infections may occur at the immediate-early stage of infection. Several studies are proposed to determine if there is site specific repression or inactivation of those genes in latently infected neurons.

描述(摘自申请者摘要)：疱疹复发单纯病毒感染折磨着数以百万计的美国人。复发性感染也是传染性病毒的重要来源。临床疾病在免疫功能低下的患者中尤为重要。在分娩过程中会复发。申请者提议使用鼠标脚垫模型研究重大分子事件的建立，单纯疱疹病毒周期的维持和重新激活阶段。这个体内研究主要集中在LAT帽区和LAT启动子，这是只有启动子在潜伏感染时活跃。这些研究包括小鼠神经中神经元特异性转录的特定机制组织以及负责保持LAT启动子的机制在所有其他启动器关闭时的延迟期间激活。关于中国石油天然气集团公司稍后内含子将进一步证明该RNA的分子性质，包括通过剪接信号的突变进一步证明它是一个内含子。其他实验可能会提供一些关于为什么它如此稳定的见解。一个病毒生命周期在生产性和潜伏性之间的根本转换感染可能发生在感染的即刻早期阶段。几个建议进行研究以确定是否存在特定部位的抑制或潜伏感染神经元中这些基因的失活。