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ROLE OF THE LAT-ICP0 LOCUS IN REGULATING HSV LATENCY

LAT-ICP0 基因座在调节 HSV 潜伏期中的作用

基本信息

批准号：
6459253
负责人：
WILLIAM P HALFORD
金额：
$ 28.49万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-15 至 2004-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6459253
关键词：
Adenoviridae antisense nucleic acid gene induction /repression herpes simplex virus 1 laboratory mouse latent virus infection tissue /cell culture transfection virus RNA virus genetics

项目摘要

DESCRIPTION (provided by applicant): Recurrent infections with herpes simplex viruses (HSV) are a significant clinical problem. Fundamental to understanding the nature of recurrent herpetic disease is determining precisely how HSV alternates between the two phases of its dual life cycle, latency and reactivation of productive infection. The LAT-ICP0 locus plays a central role in the regulation of HSV- 1 latency and reactivation. The genes that encode for the latency-associated transcripts (LATs) and infected cell polypeptide 0 (ICP0) form a continuous locus in the repeated regions of the HSV genome. Specifically, the LAT and ICP0 genes lie on opposite strands of HSV-1's double-stranded DNA genome and share a significant overlap. Thus, the abundant LATs can hybridize to 0.75 kilobases of complementary sequence in ICP0 mRNA. While the antisense arrangement of the LAT-ICP0 locus has long been recognized, the hypothesis that LAT RNAs serve as "antisense repressors" of ICP0 gene expression has not been rigorously analyzed. The juxtaposition of the LAT and ICP0 genes mirrors their opposing roles in latency. While LAT RNAs facilitate the maintenance of HSV latency, expression of ICP0 is necessary and sufficient to induce HSV-1 reactivation. Conversely, failure to express ICP0 is highly conducive to HSV genomes entering a transcriptionally repressed state. Thus, antisense repression of ICP0 mRNA translation is one mechanism by which LATs may facilitate the maintenance of latency. The goal of this research proposal is to evaluate the concept that LAT RNAs and ICP0 form a pair of mutually dependent, opposite regulators that are the yin and yang of HSV latency. Specifically, genetic evidence will be obtained to test the hypothesis that "All viral proteins that induce HSV-1 reactivation in the trigeminal ganglion cell culture model achieve this phenotype via (a) induction of ICP0, (b) suppression of LAT transcription, or (c) both."

描述（由申请人提供）：复发性单纯疱疹感染

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

ICP0 antagonizes Stat 1-dependent repression of herpes simplex virus: implications for the regulation of viral latency.

DOI：
10.1186/1743-422x-3-44
发表时间：
2006-06-09
期刊：
Virology journal
影响因子：
4.8
作者：
Halford WP;Weisend C;Grace J;Soboleski M;Carr DJ;Balliet JW;Imai Y;Margolis TP;Gebhardt BM
通讯作者：
Gebhardt BM

Herpes simplex virus 2 ICP0 mutant viruses are avirulent and immunogenic: implications for a genital herpes vaccine.