SETX, antiviral response and genetic diseases

 描述(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编排的，这些基因在感染时被特异性地诱导，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(以及它们的抗病毒活性)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”，这对宿主防御感染是必不可少的。尽管它们在感染中起到保护作用，但这些基因的长期或异常表达可能对宿主有害。因此，许多抗病毒介体的表达受到严格的监管， 在感染期间，基因的子集以不同的时间模式表达。我们计划在人类共济失调伴动眼失用症(AOA2)和Lou Gehrig病(ALS4)的患者中突变可能的解旋酶SETX的功能和作用机制。我们使用患者来源的SETX缺陷细胞的初步数据表明，SETX是控制抗病毒反应的主要参与者。我们的目标是通过多尺度分析，结合蛋白质组和基因组学方法，了解感染过程中SETX活性的调节机制。

 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.