Equine Herpesvirus EICP22 Protein in Gene Regulation

马疱疹病毒 EICP22 蛋白的基因调控

• 批准号: 6786987
• 负责人: PAUL D EBNER
• 金额: $ 4.3万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786987
• 关键词: Alphaherpesvirinae; chimeric proteins; chronic disease /disorder; disease /disorder model; gene expression; gene mutation; genetic manipulation; immediate early protein; laboratory mouse; postdoctoral investigator; protein protein interaction; regulatory gene; tissue /cell culture; virus diseases; virus protein; virus replication

DESCRIPTION (provided by applicant): The Alphaherpesvirinae subfamily is comprised of many important pathogens of humans and animals, including herpes simplex virus 1 and 2, varicella zoster virus, and Marek's disease virus. Equine herpes virus 1 (EHV) is an important, and interesting, pathogen of equines as the outcomes of infection vary from severe respiratory disease, abortigenic disease often leading to reproductive failure, severe neurological disorders, and/or latency. In the laboratory, EHV offers ideal models to investigate the molecular biology, immunology, and pathogenesis of Alphaherpesviruses. EHV infections in cell culture vary from a cytocidal infection to a state of persistent infection. The latter is mediated by defective interfering particles (DIP) whose genome encodes only three proteins, one being a unique hybrid protein derived from portions of two early regulatory genes, EICP22 and EICP2 7. In cytolytic infection, the EICP22P (protein) significantly enhances transactivation of all classes of EHV promoters by interacting with the IE (immediate early) protein. However, in persistent infection the 22/27 hybrid protein trans-represses several classes of EHV promoters. The precise mechanism(s) by which the EICP22P acts as both a trans-activator and trans-repressor remain unclear. The Applicant's overall goal is to employ models of cytocidal and persistent infection (mediated by EHV enriched for DIP) to define the contrasting functions and roles of the EICP22P in these two different outcomes of infection. Information gained from these studies may be useful in the prevention, diagnosis, and treatment of Alphaherpesvirus infections and will give insight into events leading to the establishment of persistent infection.

描述（由申请人提供）：αHerphaherpesvirinae亚家族由许多重要的人类和动物病原体组成，包括单纯疱疹病毒1和2，水痘带状疱疹病毒和Marek病毒。马疱疹病毒1（EHV）是一种重要且有趣的马的病原体，因为感染的结局因严重的呼吸道疾病而异，经常导致生殖衰竭，严重的神经系统疾病和/或潜伏期。在实验室中，EHV提供了研究α-掌病毒的分子生物学，免疫学和发病机理的理想模型。细胞培养中的EHV感染从细胞性感染到持续感染状态不等。后者是由干扰颗粒（DIP）介导的，其基因组仅编码三种蛋白质，一种是由两个早期调节基因的部分得出的独特杂交蛋白，EICP22和EICP2 7。在细胞溶解感染中，EICP22P（蛋白质）在EICP22P（蛋白质）中的交易均与EECP22P（蛋白质）相互作用促进了EICP22P（蛋白质）的早期效率（EICP22P（蛋白质）），这会促进EHV的交互作用。但是，在持续感染中，22/27杂交蛋白反式抑制几类EHV启动子。 EICP22P作为反式激活剂和反式压迫剂的确切机制尚不清楚。申请人的总体目标是采用细胞固定和持续感染模型（由EHV富含DIP介导）来定义EICP22P在这两种不同的感染结果中的对比功能和作用。从这些研究中获得的信息可能可用于预防，诊断和治疗α-鞘病毒感染，并将深入了解导致建立持续感染的事件。