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

• 批准号: 8279983
• 负责人: Jia Liu
• 金额: $ 16.08万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279983
• 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

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）： 摘要 主要研究者：刘佳 项目：1 K22 AI 099184 -01标题：含Steril Alpha基序结构域的抗病毒功能表征登录号：3399517 ================== 注意事项：本摘要摘自应用程序，未经SRA验证。当应用程序扫描过程出现问题时，提取的文本可能不正确或不完整。 ================== 这项研究旨在研究一种以前未表征的人类因子，称为无菌含基序结构域9（SAMD 9）的抗病毒功能。SAMD 9基因表达被干扰素（IFN）上调，并且当其上调时与癌细胞中的凋亡性细胞死亡相关。SAMD 9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保守。最近的基因组分析表明，人类SAMD 9中的有害突变是一种罕见的遗传疾病，称为正常磷酸盐血症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，随后在皮肤和粘膜中产生钙化肿瘤。剧烈的疼痛和频繁的感染也与发病率有关。尽管SAMD 9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然未知。最近的研究表明，人SAMD 9对许多病毒（RNA和DNA病毒）具有抗病毒功能。由于SAMD 9在所有测试的人类细胞中组成型表达，这些结果表明其作为宿主固有免疫的一部分的作用。本研究的目的是剖析这种蛋白在病毒感染过程中的作用模式。首先，通过将结合基序定位到已知的拮抗SAMD 9功能的virl因子，可以鉴定SAMD 9的功能结构域。第二，由于这些病毒采用不同的机制来拮抗SAMD 9的抗病毒功能，因此本研究的结果将详细描述它们使用感染的作用 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）。最后，也是最重要的，将进行对这些不同病毒生命周期重要的关键共同细胞功能的鉴定。这对于深入研究 了解人类细胞先天免疫机制，必须科普许多不同类型的病毒。