REPLICATION OF ROTAVIRUS RNA

轮状病毒 RNA 的复制

• 批准号: 3071011
• 负责人: JOHN T PATTON
• 金额: $ 6.94万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3071011
• 关键词: DNA directed RNA polymerase; RNA binding protein; RNA biosynthesis; Rotavirus; biological signal transduction; cell free system; crosslink; double stranded RNA; gel electrophoresis; genetic transcription; genome; high performance liquid chromatography; messenger RNA; protein purification; tissue /cell culture; virus RNA; virus replication; viruslike particle

John T. Patton is a non-tenured Assistant Professor in the Department of Microbiology and Immunology and the University of Miami School of Medicine. Dr. Patton initiated studies on the replication of the rotaviruses as an Assistant Professor at the University of South Florida in 1984 and moved to his present position in 1987. HIs research has resulted in several publications concerning rotavirus RNA replication. In 1985, he received a three-year R22 award from the NIH to pursue studies on rotavirus replication. The grant was competitively renewed in 1989 for a period of 5 years. The Department was recently awarded an NIH training grant for graduate students and post-doctorates of which the applicant is a co-P.I. The applicant's immediate goal are to further develop his research program aimed at understanding processes involved with the replication of the genome of the rotaviruses. His long term goals are to remain in academia concentrating his research efforts on the development of a research laboratory that has a significant positive impact on elucidating events in the relatively heavy teaching and committee responsibilities allowing him the opportunity to focus more energy into pursuing his research goals. The award would also provide the time required to establish research collaborations with investigators at other universities and towards the training of graduate students and post-doctorates. His application for an RCDA has the support of his chairman, Dr. J. Wayne Streilein, who has agreed to reduce Dr. Patton's departmental obligations in the event that an award is made. Rotaviruses are segmented, double-stranded RNA (dsRNA) viruses that are recognized as causative agents of acute gastroenteritis in a wide variety of animals including man. Despite their pathogenic importance, the basic molecular biology of the rotaviruses is not well understood. In previous work, Dr. Patton developed a cell-free system which supports simian rotavirus SA11 RNA replication and transcription. The synthesis of viral dsRNA in this system is asymmetrical with viral mRNA serving as the template for minus-strand synthesis. The system has allowed the identification and description of subviral particles that synthesize dsRNA (replicase particles). The data indicate that replicase particles are heterogenous with respect to size, density and protein composition. Replicase particles appear to share in common the structural proteins VP1 and VP3 and the nonstructural proteins NS35, NS34 and NS26. Some replicase particles, in addition to the common proteins, also contain VP2 while others contain VP2 and VP6. This heterogeneity apparently arises from the fact that as replicase particles synthesize dsRNA, they concurrently undergo morphogenesis into single-shelled particles by the sequential addition of first VP2 and then VP6 to particles that contain the structural proteins VP1 and VP3. The focus of the research proposed by Dr. Patton is to characterize more completely the structure of rotavirus replicase particles, the function of proteins associated with replicase particles, and the recognition signals of viral mRNA that allow their replication by replicase particles.

约翰·帕顿（John T. Patton 微生物学和免疫学以及迈阿密大学医学院。 Patton博士开始了关于轮状病毒复制的研究 1984年在南佛罗里达大学的助理教授移至 他在1987年目前的职位。他的研究导致了几个 有关轮状病毒RNA复制的出版物。 1985年，他收到了 NIH的三年R22奖旨在进行轮状病毒研究 复制。 该赠款在1989年进行了竞争性续签，为期5期 年。 该部门最近获得了NIH培训补助金 申请人的研究生和专业人士是co-i。 申请人的近期目标是进一步制定他的研究计划 旨在理解与复制相关的过程 轮状病毒的基因组。 他的长期目标是留在学术界 将他的研究工作集中在研究的发展上 实验室对阐明事件有重大积极影响 相对沉重的教学和委员会责任使他 有机会将更多的精力集中在追求他的研究目标上。 这 奖项还将提供建立研究所需的时间 与其他大学的调查员合作 培训研究生和专业后。 他申请 RCDA得到了主席J. Wayne Streilein博士的支持， 同意减少帕顿博士的部门义务，如果 奖励。 轮状病毒是分段的，双链RNA（dsRNA）病毒的 被公认为多种急性胃肠炎的病因 包括人在内的动物。 尽管具有病原的重要性，但基本 轮状病毒的分子生物学尚不清楚。 在上一个 工作，Patton博士开发了一个无细胞的系统，该系统支持Simian 轮状病毒SA11 RNA复制和转录。 病毒的合成 该系统中的dsRNA不对称，病毒mRNA作为 负链合成的模板。 该系统允许 合成DSRNA的次病毒颗粒的识别和描述 （复制酶颗粒）。 数据表明复制酶颗粒是 关于大小，密度和蛋白质组成的异质。 复制酶颗粒似乎共有共同的结构蛋白VP1 和VP3以及非结构蛋白NS35，NS34和NS26。 一些复制酶 除了普通蛋白外，颗粒还包含VP2 其他包含VP2和VP6。 这种异质性显然来自 作为复制酶粒子合成dsRNA的事实，它们同时 通过顺序将形态发生成单壳颗粒 将第一个VP2添加到包含结构的粒子中 蛋白质VP1和VP3。 Patton博士提出的研究的重点是 更完整地表征轮状病毒复制酶的结构 颗粒，与复制酶颗粒相关的蛋白质的功能， 以及病毒mRNA的识别信号，允许其复制 复制酶颗粒。