Influenza virus receptors on human airway epithelial cells

人呼吸道上皮细胞上的流感病毒受体

基本信息

批准号：
9233896
负责人：
JAMES C PAULSON
金额：
$ 58.58万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-03 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9233896
关键词：
Address Air Avian Influenza A Virus Biological Biological Assay Birds Bronchi Cadaver Cell Culture Techniques Cell Line Cells Consensus Custom Data Analyses Digestion Domestic Fowls Engineering Enzymes Epithelial Cells Exhibits Hemagglutinin Human Individual Infection Influenza Influenza A Virus, H5N1 Subtype Influenza A Virus, H7N9 Subtype Influenza Hemagglutinin Knowledge Laboratories Libraries Light Link Liquid substance Lung Mass Spectrum Analysis Methods Methylation Modeling Mutation N-acetyllactosamine Neuraminidase Nose Patients Polysaccharides Population Property Proteins Recombinants Risk Role Sialic Acids Specificity Specimen Structure Surveys Techniques Time Trachea Variant Virus Virus Receptors airway epithelium base individual patient influenzavirus interest mortality novel pandemic disease preference public health relevance receptor receptor binding sialic acid receptor tool transmission process volunteer

项目摘要

DESCRIPTION (provided by applicant): Influenza virus causes worldwide seasonal infections and occasional pandemics with high mortality rate. Human viruses are known to have a preference for 2-6 linked sialic acids (NeuAc2-6Gal), while avian viruses exhibit a preferenc for 2-3 linked sialic acids (NeuAc2-3Gal). This difference in receptor specificity is widely considered a major species barrier for transmission of avian viruses in the human population. Although this binary model of receptor specificity has been useful, it belies the true complexity o sialic acid containing glycans on host cells, it has becoming increasingly limiting since recent influenza viruses exhibit mixed specificities that are not distinct from avian viruses using standard assays of assessing receptor specificity. The use of glycan microarrays with dozens of 2-3 and 2-6 linked glycans has revealed that influenza viruses exhibit dramatic differences i their ability to recognize individual glycans within those broad groups. However, interpretation of these findings is confounded by the fact that there is little information on the types of glycans that are actually present on human airway epithelium, and whether the relevant glycans are represented on glycan microarrays. To address this gap in knowledge, we intend to 1) analyze the glycan structures on human airway epithelial cells, 2) to build a synthetic library of these glycans for constructing a custom glycan microarray, and 3) to evaluate the specificity of human influenza virus hemagglutinins (HAs) and neuraminidases (NAs) to identify receptor-binding properties that support their ability to transmit in humans. This information will identify recepto determinants on the human airway that are shared by human influenza viruses that transmit in the human population, and shed light on properties of the HA and NA that contribute to pandemic risk of influenza viruses from avian viruses that occasionally infect humans.

描述（由适用提供）：流感病毒引起全球季节性感染和偶尔的大流行病，其死亡率很高。已知人类病毒偏爱2-6链接的唾液酸（Neuac2-6Gal），而鸟类病毒则表现出对2-3连接的唾液酸（neuac2-3gal）的首选。这种受体特异性的这种差异被广泛认为是人群中禽病毒传播的主要物种障碍。尽管这种受体特异性的二元模型很有用，但它掩盖了含有聚糖的真正复杂性o宿主细胞上的sial酸，但它已经变得越来越限制，因为使用评估受体特异性的标准评估，这些近期存在的混合规格与禽病毒并未与鸟类病毒不同。使用数十个2-3和2-6连接的聚糖的聚糖微阵列的使用表明，影响病毒暴露了戏剧性差异I I他们能够在这些广泛群体中识别单个聚糖的能力。但是，解释这些发现令人困惑，因为关于人类气道上皮上实际存在的聚糖类型的信息很少，以及是否在聚糖微阵列上代表了相关的聚糖。 To address this gap in knowledge, we intend to 1) analyze the glycan structures on human airway epithelial cells, 2) to build a synthetic library of these glycans for constructing a custom glycan microarray, and 3) to evaluate the specificity of human influence viruses hemagglutinins (HAs) and neurominidases (NAs) to identify receptor-binding properties that support their ability to transmit in humans.这些信息将识别人类呼吸道上的受体确定因素，这些因素是由人类人口传播的人类影响病毒共享的，并阐明了HA和NA的性质，这会导致偶尔感染人类的禽病毒受影响病毒的大流行风险。