REPLICATION OF ROTAVIRUS RNA

轮状病毒 RNA 的复制

• 批准号: 2057011
• 负责人: JOHN T PATTON
• 金额: $ 6.86万
• 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/2057011
• 关键词: 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; replicase; 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·T·巴顿 (John T. Patton) 是该系的非终身教授。 微生物学和免疫学以及迈阿密大学医学院。 巴顿博士发起了轮状病毒复制的研究 1984年任南佛罗里达大学助理教授，后转学到 他于 1987 年担任现职。HI 的研究取得了多项成果 有关轮状病毒RNA复制的出版物。 1985年，他获得了 NIH 颁发的为期三年的 R22 奖用于轮状病毒研究 复制。 该补助金于 1989 年竞争性地延长，为期 5 年 年。 该部门最近获得了 NIH 培训补助金 申请人担任co-P.I.的研究生和博士后 申请人的近期目标是进一步发展他的研究计划 旨在了解与复制有关的过程 轮状病毒的基因组。 他的长期目标是留在学术界 将他的研究精力集中在一项研究的发展上 对阐明事件具有重大积极影响的实验室 相对繁重的教学和委员会职责使他能够 有机会集中更多精力追求他的研究目标。 这 奖项还将提供建立研究所需的时间 与其他大学的研究人员合作并致力于 研究生和博士后培养。 他的申请 RCDA 得到了主席 J. Wayne Streilein 博士的支持，他曾 同意减少巴顿博士的部门义务，如果 奖项已颁发。 轮状病毒是分段双链 RNA (dsRNA) 病毒， 被认为是多种急性胃肠炎的病原体 包括人类在内的动物。 尽管它们具有重要的致病性，但基本的 轮状病毒的分子生物学尚不清楚。 在之前的 巴顿博士开发了一种支持猿猴的无细胞系统 轮状病毒 SA11 RNA 复制和转录。 病毒的合成 该系统中的 dsRNA 是不对称的，病毒 mRNA 作为 负链合成的模板。 系统已允许 合成 dsRNA 的亚病毒颗粒的鉴定和描述 （复制粒子）。 数据表明复制酶颗粒 在大小、密度和蛋白质组成方面具有异质性。 复制酶颗粒似乎具有共同的结构蛋白 VP1 VP3 和非结构蛋白 NS35、NS34 和 NS26。 一些复制酶 颗粒中除了常见的蛋白质外，还含有VP2，同时 其他包含 VP2 和 VP6。 这种异质性显然是由 事实上，当复制酶颗粒合成 dsRNA 时，它们同时 通过连续的形态发生形成单壳粒子 首先将 VP2 添加到包含结构的颗粒中，然后添加 VP6 蛋白质VP1和VP3。 巴顿博士提出的研究重点是 更全面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。