Influenza virus receptors on human airway epithelial cells

人呼吸道上皮细胞上的流感病毒受体

• 批准号: 8963149
• 负责人: JAMES C PAULSON
• 金额: $ 31.69万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 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/8963149
• 关键词: Address; Air; Avian Influenza A Virus; Biological; Biological Assay; Birds; Bronchi; Cadaver; Cell Culture Techniques; Cell Line; Cells; Consensus; Cultured Cells; Custom; Data; Digestion; Domestic Fowls; Engineering; Enzymes; Epithelial Cells; Exhibits; Hemagglutinin; Human; Human Virus; 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; 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; influenzavirus; interest; lactosamine; mortality; novel; pandemic disease; preference; public health relevance; receptor; receptor binding; sialic acid receptor; tool; transmission process; volunteer

 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（由申请人提供）：已知人类病毒偏爱 α2-6 连接唾液酸（NeuAcα2-6Gal），而禽病毒则表现出偏爱性。偏好 α2-3 连接的唾液酸 (NeuAcα2-3Gal) 这种受体特异性的差异被广泛认为是传播病毒的主要物种障碍。尽管这种受体特异性的二元模型很有用，但它掩盖了宿主细胞上含唾液酸聚糖的真正复杂性，并且由于最近的流感病毒表现出与禽类没有区别的混合特异性，因此它变得越来越具有局限性。使用评估受体特异性的标准测定法对病毒进行评估 使用具有数十个 α2-3 和 α2-6 连接聚糖的聚糖微阵列表明，流感病毒在识别广泛的单个聚糖的能力方面表现出巨大差异。然而，群体的解释。 这些发现令人困惑的是，关于人类气道上皮上实际存在的聚糖类型以及相关聚糖是否在聚糖微阵列上出现的信息很少，为了解决这一知识空白，我们打算 1) 分析。人呼吸道上皮细胞上的聚糖结构，2) 构建这些聚糖的合成文库，用于构建定制聚糖微阵列，3) 评估人流感病毒的特异性血凝素 (HA) 和神经氨酸酶 (NA) 来识别支持其在人类中传播能力的受体结合特性。该信息将识别人类呼吸道上的受体决定因素，这些受体决定因素是在人群中传播和传播的人类流感病毒所共有的。阐明 HA 和 NA 的特性，这些特性导致偶尔感染人类的​​禽流感病毒产生大流行风险。