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Characterization of Antiviral Functions of Sterile Alpha Motif-Containing Domain

含有不育α基序的结构域的抗病毒功能的表征

基本信息

批准号：
8672591
负责人：
Jia Liu
金额：
$ 10.74万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-15 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8672591
关键词：
Affect Antiviral Agents Antiviral Response Apoptotic Attention Autoimmune Diseases Binding Biological Process Calcified Calcinosis Cell Death Cell physiology Cells Chronic Cutaneous DNA Viruses Disease Drug Targeting Dystrophic Calcification Ebola virus Eukaryota Frankfurt-Marburg Syndrome Virus Gene Expression General Population Generations Genes Genomics Goals Hereditary Disease Herpesvirus 1 Human Immune Immune response Immune system Immunity Infection Inflammation Inflammatory Inflammatory Response Inherited Interferons Knowledge Lead Length Life Life Cycle Stages Malignant Neoplasms Maps Modeling Modification Morbidity - disease rate Mucous Membrane Mutation Myxoma virus Names Pain Pathway interactions Patients Phase Transition Phosphorylation Play Poxviridae Process Proteins Proteomics RNA Viruses Regulation Role SAM Domain Scanning Signal Transduction Skiing Staging Sterility Test Result Text Therapeutic Transcriptional Regulation Viral Viral Physiology Virus Virus Diseases Yeasts abstracting calcification cancer cell career coping effective therapy experience gene function genetic analysis insight pathogen protein degradation response secondary infection tumor viral DNA viral RNA

项目摘要

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.

描述（由申请人提供）：抽象的负责人：LIU、JIA 项目：1K22AI099184-01 标题：含 Steril Alpha 基序的结构域抗病毒功能的表征登录号：3399517 ================= 注意：此摘要是从申请中提取的，未经 SRA 验证。当申请扫描过程出现问题时，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先前未表征的人类因子的抗病毒功能，该因子称为无菌 ¿ 基序包含结构域 9 (SAMD9)。 SAMD9 基因表达受干扰素 (IFN) 上调，并且当其上调时与癌细胞中的细胞凋亡相关。 SAMD9 基因在脊椎动物中高度保守，但在低等真核生物（例如酵母）中则不然。最近的基因组分析表明，人类 SAMD9 的有害突变导致一种罕见的遗传病，称为正磷酸盐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，随后在滑雪板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有关。尽管 SAMD9 在炎症反应过程中的重要作用已被多次提出，但该基因的生物学功能仍然未知。最近的研究表明，人类 SAMD9 对多种病毒（RNA 和 DNA 病毒）具有抗病毒功能。由于 SAMD9 在所有测试的人类细胞中组成型表达，因此这些结果表明其作为宿主内在免疫的一部分的作用。这项研究的目的是剖析这种蛋白质在病毒感染期间的作用模式。首先，通过将结合基序映射到拮抗SAMD9功能的已知virl因子，可以鉴定SAMD9的功能域。其次，由于这些病毒应用不同的机制来拮抗 SAMD9 的抗病毒功能，本研究的结果将详细描述它们利用感染的作用模型由两种 DNA 病毒：粘液瘤病毒 (MYXV) 和 1 型单纯疱疹病毒 (HSV-1) 组成。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。这对于深入研究至关重要了解必须应对许多不同类型病毒的人类细胞先天免疫机制。