Construction of a Respiratory Syncytial Virus Replicon

描述（由申请方提供）：呼吸道合胞病毒（RSV）是婴儿最重要的呼吸道病原体，尤其是早产儿。它也是老年人和免疫抑制疾病的重要原因。没有疫苗可用于保护免受RSV感染，并且“处于危险中”的婴儿目前通过被动免疫治疗。预防RSV感染或改善其的有效小分子药物将具有很大的价值。第一阶段的目标是开发一种新的“复制子”系统，用于筛选潜在的抗病毒化合物。RSV复制子将是缺失其三个糖蛋白基因的遗传修饰的病毒基因组。复制子将含有耐药性基因以选择含有复制子的细胞和标记基因以容易地测定病毒复制和基因表达。该系统将为快速筛选抑制RSV基因组复制、mRNA转录或翻译中涉及的任何途径的化合物提供有用的分子工具。RSV复制子对于RSV的遗传学研究和使用RSV作为载体的努力也将是有价值的。

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is the most important respiratory pathogen in infants, especially those born prematurely. It is also an important cause of disease in the elderly and immunosuppressed. There is no vaccine available to protect against RSV and "at risk" infants are presently treated by passive immunization. An effective small molecule drug that prevents RSV infection or ameliorates it would be of great value. The goal of this Phase I proposal is to develop a novel "replicon" system for screening potential antiviral compounds. The RSV replicon will be a genetically modified viral genome missing its three glycoprotein genes. The replicon will contain a drug-resistance gene to select cells that contain the replicon and a marker gene to easily assay virus replication and gene expression. This system will provide a useful molecular tool for rapid screening of compounds that inhibit any pathway involved in RSV genome replication, mRNA transcription, or translation. An RSV replicon will also be valuable for genetic studies of RSV and in efforts to use RSV as a vector.