FUNCTIONS OF THE PROTEINS OF HUMAN RESPIRATORY SYNCYTIAL VIRUS

人呼吸道合胞病毒蛋白质的功能

• 批准号: 6431577
• 负责人: PETER LEON COLLINS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431577
• 关键词: DNA directed RNA polymerase; RNA biosynthesis; genetic transcription; microorganism culture; microorganism growth; nucleocapsid; phosphoproteins; plasmids; posttranslational modifications; protein structure function; replicase; respiratory syncytial virus; tissue /cell culture; transfection; virus RNA; virus envelope; virus genetics; virus protein; virus replication

Human respiratory syncytial virus (RSV) is an enveloped RNA-containing virus of Family Paramyxoviridae, Order Mononegavirales, the nonsegmented negative strand RNA viruses. RSV is the most important viral agent of pediatric respiratory tract disease worldwide but lacks an approved vaccine or effective antiviral therapy. Other mononegaviruses include measles, mumps, rabies and Ebola viruses, and hence study of the group is of interest in general. We previously showed that the RSV genome is a single negative strand of RNA of 15,222 nucleotides that encodes 10 major mRNAs and 11 proteins. It thus is one of the more complex mononegaviruses. The purpose of this project is to identify the functions of the viral proteins and to reconstruct events in the viral growth cycle under conditions where they can be more readily studied. Part of these studies involves a minireplicon system, in which an short analog of the genome or its antigenome replicative intermediate is expressed intracellularly from a transfected plasmid and complemented by proteins supplied from other plasmids. Another approach involves infectious recombinant virus bearing mutations in relevant genes. Knowledge of the functions of the proteins is important for a basic understanding of this important human pathogen and for the design of live-attenuated recombinant vaccine viruses. One of the RSV proteins, the M2-1 protein, was identified as a novel transcription antitermination protein. Another protein, M2-2, that is expressed from a separate open reading frame from the same mRNA was identified as a novel RNA regulatory protein.

人呼吸道合胞病毒 (RSV) 是副粘病毒科、单链病毒目、不分节段负链 RNA 病毒，是一种含有包膜 RNA 的病毒。 RSV 是全世界儿科呼吸道疾病最重要的病毒病原体，但缺乏批准的疫苗或有效的抗病毒治疗。其他单负病毒包括麻疹、腮腺炎、狂犬病和埃博拉病毒，因此对该组的研究普遍引起人们的兴趣。我们之前表明，RSV 基因组是一条由 15,222 个核苷酸组成的 RNA 负链，编码 10 个主要 mRNA 和 11 种蛋白质。因此，它是更复杂的单负病毒之一。该项目的目的是确定病毒蛋白的功能，并在更容易研究的条件下重建病毒生长周期中的事件。这些研究的一部分涉及微型复制子系统，其中基因组或其反基因组复制中间体的短类似物从转染的质粒在细胞内表达，并由其他质粒提供的蛋白质补充。另一种方法涉及相关基因带有突变的感染性重组病毒。了解蛋白质的功能对于基本了解这种重要的人类病原体以及设计减毒活重组疫苗病毒非常重要。 RSV 蛋白之一 M2-1 蛋白被鉴定为一种新型转录抗终止蛋白。另一种蛋白质 M2-2 是由同一 mRNA 的独立开放阅读框表达的，被鉴定为一种新型 RNA 调节蛋白。