Measles virus C protein: polymerase interactions and innate immunity evasion

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

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.