FUNCTIONS OF THE PROTEINS OF HUMAN RESPIRATORY SYNCYTIAL VIRUS

人呼吸道合胞病毒（RSV）是一种含包膜RNA的单病毒目副粘病毒科非分节负链RNA病毒。RSV是全球儿童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。其他单链病毒包括麻疹、腮腺炎、狂犬病和埃博拉病毒，因此对这类病毒的研究具有普遍意义。我们之前的研究表明，RSV基因组是一条15222个核苷酸的单负链RNA，编码10个主要mrna和11个蛋白质。因此它是较复杂的单胞病毒之一。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，其中基因组的短类似物或其抗基因组复制中间物在转染的质粒中在细胞内表达，并由其他质粒提供的蛋白质补充。另一种方法涉及携带相关基因突变的传染性重组病毒。了解蛋白质的功能对于基本了解这一重要的人类病原体和设计减毒重组活疫苗病毒非常重要。其中一种RSV蛋白M2-1蛋白被鉴定为一种新的转录抗终止蛋白。另一种蛋白M2-2，从同一mRNA的单独开放阅读框中表达，被鉴定为一种新的RNA调节蛋白。

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.