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In vivo relevance of the Schlafen-mediated innate immune mechanism in flavivirus infection

黄病毒感染中 Schlafen 介导的先天免疫机制的体内相关性

基本信息

批准号：
10629718
负责人：
Manuel Llano
金额：
$ 15.14万
依托单位：
UNIVERSITY OF TEXAS EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-22 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10629718
关键词：
3T3 Cells Adult Biological Markers Biomedical Research Bioterrorism Cell Line Cells Classification Clinical Codon Nucleotides Cytomegalovirus Dengue Virus Disease susceptibility Education Ethnic Population Family Flavivirus Flavivirus Infections Genes Glioblastoma Hispanic Human Immune response Immunocompetent Impairment In Vitro Infection Interferon Type I Interferons Investigation Knowledge Length Mammals Measurement Measures Mediating Molecular Mus Mutagenesis NIH 3T3 Cells NIH Mouse Organ Orthologous Gene Outcome Population Predisposition Proteins Reporting Research Research Training Rift Valley fever virus Role Severity of illness Specificity Structural Protein Students System Time Transfer RNA Underrepresented Populations Vesicular stomatitis Indiana virus Viral Viral Load result Viral Physiology Virion Virus Virus Diseases Virus Replication West Nile viral infection West Nile virus Zika Virus biomarker identification cell type cytokine experimental study graduate student human model human pathogen in vivo in vivo evaluation innate immune mechanisms knock-down member mouse model new therapeutic target novel overexpression prevent response therapeutic target undergraduate student vaccine access

项目摘要

ABSTRACT Flaviviruses are important human pathogens including viruses such as West Nile, dengue, and Zika. No specific treatments or vaccines are available against these infections, and no biomarkers exist that allow predicting their outcome, characterized by important clinical variability. Understanding innate antiviral immune responses against flaviviruses, could lead to the identification of disease susceptibility biomarkers and therapeutic targets. We recently demonstrated that the type I interferon-stimulated protein Schlafen 11 (SLFN11) is a novel and potent flavivirus restriction factor. In this application we aim to define, at the molecular level, several aspects of the mechanism of action of SLFN11 and determine the anti-flavivirus activity of other members of the SLFN family, as well as the in vivo relevance of this defense system. Therefore, this investigation is highly relevant and will significantly advance our understanding of the antiviral mechanism of action of SLFN proteins, which is currently unknown.

摘要黄病毒是重要的人类病原体，包括西尼罗河病毒、登革热病毒和寨卡病毒。不是针对这些感染有特定的治疗方法或疫苗可用，而且没有生物标记物可以预测他们的结果，以重要的临床变异性为特征。了解先天抗病毒免疫对黄病毒的反应，可能导致识别疾病易感性生物标志物和治疗靶点。我们最近证明了I型干扰素刺激蛋白Schlafen 11 (SLFN11)是一种新的有效的黄病毒限制因子。在本申请中，我们的目标是在分子上定义水平，SLFN11作用机制的几个方面，并确定其他化合物的抗黄病毒活性 SLFN家族的成员以及这一防御系统的体内相关性。因此，这研究具有很高的相关性，并将极大地促进我们对抗病毒机制的理解 SLFN蛋白的作用，目前尚不清楚。