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Measles virus C protein: polymerase interactions and innate immunity evasion

麻疹病毒 C 蛋白：聚合酶相互作用和先天免疫逃避

基本信息

批准号：
9223834
负责人：
ROBERTO B. CATTANEO
金额：
$ 23.85万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9223834
关键词：
Antiviral Agents Antiviral Response Attenuated Back Cell Line Cells Cellular Stress Response Cessation of life Characteristics Co-Immunoprecipitations Code Color Complex Defective Viruses Development Double-Stranded RNA Enzymes Family Generations Genes Genetic Transcription Genome Hemagglutinin Homologous Protein Human Immune Evasion Infection Initiator Codon Innate Immune Response Interferons Intergenic Sequence Knowledge Light Measles Measles virus Measures Mediating Messenger RNA Monkeys Morbillivirus Mutagenesis Natural Immunity Nucleocapsid Nucleotides Oranges Paramyxoviridae Paramyxovirus Pathway interactions Peripheral Blood Mononuclear Cell Phosphoproteins Polymerase Population Production Proteins Public Health RNA RNA Editing RNA I RNA Viruses RNA chemical synthesis Reading Frames Recombinants Recruitment Activity Reporter Reporting Respiratory Tract Infections Site Structure Testing Textbooks Transcript Translating Viral Viral Genome Virulence Virulence Factors Virus Virus Diseases Virus Replication base biological adaptation to stress cancer cell citrate carrier deletion analysis dsRNA adenosine deaminase eIF-2 Kinase genetic approach genomic RNA mutant oncolytic vector particle protein expression protein kinase R response viral RNA

项目摘要

The small basic C protein is a virulence factor that contributes to innate immunity evasion of Paramyxoviridae, but its mechanisms of action are incompletely understood. Focusing on the measles virus (MeV) C protein, we have shown that, first, it promotes accurate RNA synthesis by limiting the production of defective-interfering (DI) RNA. Second, we show here that C is recruited to sites of replication only when the large (L) subunit of the viral polymerase is present, suggesting the possibility of direct L-C protein interactions. We seek now to characterize the mechanisms of C protein action. The central hypothesis is that it is a co-factor that regulates RNA synthesis and enhances polymerase accuracy, thereby limiting the generation of DI RNA and the activation of innate immunity. The specific aims are, first, to assess how C interacts with L to promote polymerase accuracy. Second, to characterize how the C protein regulates viral genome replication and transcription. Third, to assess whether transcripts produced by copy-back DI RNAs are the main activator of the interferon response.

小碱性C蛋白是副粘病毒科的一种毒力因子，有助于逃避先天免疫，但其作用机制尚不完全清楚。针对麻疹病毒（MeV）C蛋白，我们已经表明，首先，它通过限制缺陷干扰RNA的产生来促进准确的RNA合成。 (DI)核糖核酸其次，我们在这里表明，C被招募到复制位点时，只有大（L）亚基的复制，存在病毒聚合酶，表明直接L-C蛋白相互作用的可能性。我们现在寻求描述C蛋白的作用机制。中心假设是，它是一个辅助因子，调节 RNA合成和提高聚合酶的准确性，从而限制DI RNA的产生和DNA的合成。先天免疫的激活。具体的目的是，首先，评估C如何与L相互作用，以促进聚合酶准确性。其次，为了表征C蛋白如何调节病毒基因组复制，转录。第三，为了评估由复制回DI RNA产生的转录物是否是转录因子的主要激活剂，干扰素反应