FUNCTIONS OF THE PROTEINS OF HUMAN RESPIRATORY SYNCYTIAL VIRUS

人呼吸道合胞病毒(RSV)是副粘病毒科、单核病毒目、非节段性负链RNA病毒的囊膜病毒。RSV是全球儿童呼吸道疾病最重要的病毒剂，但缺乏经批准的疫苗或有效的抗病毒治疗。其他单粒病毒包括麻疹、流行性腮腺炎、狂犬病和埃博拉病毒，因此对该群体的研究总体上是有兴趣的。我们以前证明了RSV基因组是一个由15,222个核苷酸组成的单链负链RNA，编码10个主要的mRNAs和11个蛋白质。因此，它是一种更复杂的单核细胞病毒。这个项目的目的是确定病毒蛋白的功能，并在更容易研究它们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，在该系统中，基因组或其反基因组复制中间体的短类似物在细胞内表达，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。了解这些蛋白质的功能对于基本了解这种重要的人类病原体和设计活的减毒重组疫苗病毒很重要。其中，M2-1蛋白被鉴定为一种新的转录抗终止蛋白。另一种蛋白质M2-2是从同一个mRNA的单独开放阅读框中表达的，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.