SETX, antiviral response and genetic diseases

 描述（由申请人提供）：对感染的先天免疫反应代表了对入侵病原体的第一种细胞防御。这种反应是由一组复杂的基因精心策划的，这些基因在感染时特异性诱导，包括细胞因子、趋化因子以及其他重要的抗病毒介质。虽然许多这些感染诱导基因的功能（及其抗病毒活性）仍然难以捉摸，但它们的调控表达 在细胞中建立一种“抗病毒状态”，这是宿主防御感染所必需的。尽管它们在感染中具有保护作用，但这些基因的长期或异常表达可能对宿主有害。因此，许多抗病毒介质的表达受到严格调节， 在感染期间，基因的子集以不同的时间模式表达。我们计划在这里的功能和作用机制的推定的解旋酶SETX，这是突变的人类患者共济失调与眼用不能症（AOA2）和一个子集的Lou Gehrig病（ALS4）。我们的初步数据，使用患者源性SETX缺陷细胞表明，SETX是一个主要的球员在控制抗病毒反应。我们的目标是通过多尺度分析，包括整合蛋白质组学和基因组学方法的机制，在感染过程中调节SETX活性的理解。

 DESCRIPTION (provided by applicant): The innate immune response to infection represents the first cellular defense against invading pathogens. This response is orchestrated by a complex cohort of genes that are specifically induced upon infection and include cytokines, chemokines as well as other important anti­viral mediators. While the function of many of these infection­induced genes (and their antiviral activity) remains elusive, their regulated expression establishes an 'antiviral state' in the cell that is essential for the host defense to infections. Despite their protective role in infection, prolonged or aberrant expression of such genes can be deleterious to the host. As such, the expression of many antiviral mediators is strictly regulated, with subsets of genes expressed in distinct temporal patterns during infection. We plan here to characterize the function and mechanism of action of the putative helicase SETX, which is mutated in human patients with ataxia with oculomotor apraxia (AOA2) and a subset of Lou Gehrig's disease (ALS4). Our preliminary data using patients­derived SETX deficient cells indicate that SETX is a major player in controlling the antiviral response. We aim at understanding through a multiscale analysis involving integrative proteomic and genomic approach the mechanism regulating SETX activity during infection.