Characterization of Antiviral Functions of Sterile Alpha Motif-Containing Domain

描述(由申请人提供)： 摘要 Pi：Liu，JIA项目：1K22AI099184-01标题：含Steril Alpha基序的抗病毒功能研究登录号：3399517 = 注意：此摘要摘自应用程序，未经SRA校对。如果应用程序扫描过程有问题，提取的文本可能不正确或不完整。 = 这项拟议的研究旨在研究一种以前未被描述的人类因子，称为不育基序包含结构域9(SAMD9)的抗病毒功能。SAMD9基因的表达受干扰素(IFN)的上调，当其上调时与癌细胞的凋亡细胞死亡有关。SAMD9基因在脊椎动物中高度保守，但在酵母等低等真核生物中不存在。最近的基因组分析表明，人类SAMD9的有害突变导致了一种罕见的遗传性疾病，称为正常磷酸盐血症性家族性肿瘤钙质沉着症(NFTC)。NFTC患者在生命早期经历慢性炎症，随后在滑膜和粘膜中产生钙化肿瘤。持续的疼痛和频繁的感染也与发病率有关。虽然SAMD9在炎症反应中的重要作用已被反复提出，但该基因的生物学功能仍不清楚。最近的研究表明，人SAMD9对多种病毒(RNA和DNA病毒)具有抗病毒作用。由于SAMD9在所有被测试的人类细胞中都有结构性表达，这些结果表明它是宿主固有免疫的一部分。这项研究的目的是剖析该蛋白在病毒感染过程中的作用模式。首先，通过将结合基序映射到已知的拮抗SAMD9功能的病毒因子上，可以识别SAMD9的功能结构域。其次，由于这些病毒应用不同的机制来拮抗SAMD9的S的抗病毒功能，本研究的结果将提供关于它们利用感染作用的详细描述 模型由两种DNA病毒，粘液瘤病毒(MYXV)和单纯疱疹病毒1型(HSV-1)建立。最后，也是最重要的是，将对这些不同的病毒生命周期重要的关键共同细胞功能进行鉴定。这对于深入了解 了解必须应对多种不同类型病毒的人类细胞先天免疫机制。

DESCRIPTION (provided by applicant): Abstract PI: LIU, JIA Project: 1K22AI099184-01 Title: Characterization of Antiviral Functions of Steril Alpha Motif-Containing Domain Accession Number: 3399517 ================== NOTICE: THIS ABSTRACT WAS EXTRACTED FROM APPLICATION AND HAS NOT BEEN PROOFED BY AN SRA.WHEN THERE ARE PROBLEMS WITH THE APPLICATION SCANNING PROCESS, THE EXTRACTED TEXT MAY BE INCORRECT OR INCOMPLETE. ================== This proposed study is aimed at investigating the antiviral functions of a previously un- characterized human factor, called sterile ¿ motif-containing domain 9 (SAMD9). SAMD9 gene expression is up-regulated by interferons (IFNs), and is associated with apoptotic cell death in cancer cells when it is up-regulated. SAMD9 gene is highly conserved among vertebrate species, but not in lower eukaryotes, such as yeast. Recently genomic analyses showed deleterious mutations in human SAMD9 are responsible for a rare genetic disease called Normophosphatemic Familial Tumoral Calcinosis (NFTC). Patients with NFTC experience chronic inflammation early in their life, followed by the generation of calcified tumors in the ski and mucosa. Incessant pain and frequent infections are also associated with the morbidity. Although the essential role of SAMD9 during inflammatory responses has been repeatedly suggested, the biological functions of this gene remain unknown. Recent studies showed that human SAMD9 has anti-viral functions against numbers of viruses (RNA and DNA viruses). Because SAMD9 is constitutively expressed in all human cells tested, these results suggest its role as a part of host intrinsic immunity. The goal of this study is to dissect the mode of action f this protein during viral infections. First of all, through mapping the binding motifs to known virl factors that antagonize SAMD9 functions, the function domains of SAMD9 can be identified. Second, as these viruses apply different mechanisms to antagonize SAMD9's antiviral functions, results from this study will provide detail descriptions on their action using infection models by two DNA viruses, myxoma virus (MYXV) and herpes simplex virus type 1 (HSV-1). Finally and most importantly, identification of the key common cellular functions which are important to these disparate viral life cycles will be carried out. This is crucial for an in-depth understanding of human cellular innate immune mechanisms that must cope with viruses of many distinct types.