Influenza host specific glycan motif identification through systems biology

通过系统生物学鉴定流感宿主特异性聚糖基序

• 批准号: 10092924
• 负责人: XIUFENG HENRY WAN
• 金额: $ 19.98万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092924
• 关键词: Affect; Animals; Antibodies; Area; Avian Influenza A Virus; Binding; Binding Sites; Biological; Biosensor; Birds; Canis familiaris; Code; Complex; Computing Methodologies; Data; Data Set; Development; Domestic Fowls; Equus caballus; Family suidae; Goals; Growth; Hemagglutinin; Human; Immune Sera; Infection; Influenza; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza prevention; Knowledge; Learning; Lectin; Life; Link; Mammals; Methods; Molecular; Monitor; Mutation; National Institute of Allergy and Infectious Disease; Natural History; Pathogenesis; Performance; Play; Polysaccharides; Property; Proteins; Public Health; Research; Resources; Risk; Role; Sea; Sialic Acids; Signal Transduction; Slide; Strategic Planning; Streptavidin; Structure; Systems Biology; Technology; Testing; Tissues; Trees; Tropism; United States National Institutes of Health; Validation; Variant; Virus Diseases; Zoonoses; base; carbohydrate receptor; carbohydrate structure; computerized tools; design; experimental study; flu transmission; improved; in silico; influenza infection; influenza virus vaccine; large datasets; learning strategy; machine learning method; microorganism; multi-task learning; multitask; novel; pathogen; prevent; rapid test; receptor; receptor binding; respiratory; response; swine influenza; tissue tropism; tool; transmission process; universal influenza vaccine; viral transmission; wild bird

Project Summary Influenza A viruses (IAVs) have caused large losses of life around the world and continue to present a great public health challenge. IAVs can cause infections in birds, sea mammals, lower mammals (e.g., pigs, dogs, and horses), and humans. Previous studies have demonstrated that the structures of the carbohydrate receptors determine influenza host and tissue tropisms. Thus, it is necessary to understand the receptor- binding properties for IAVs and monitor changes to them, especially for IAVs at the animal–human interface. However, this understanding is hampered by our lack of detailed knowledge of IAV glycan substructures; most of our knowledge is limited to SA2,3Gal-like and SA2,6Gal-like structures. The goals of this project are to develop and validate a machine learning method to identify host-specific glycan substructures for IAVs by using glycan array data and to identify and validate the glycan motifs associated with the host tropisms of IAVs, including those for zoonotic IAVs. The study will focus on natural hosts of IAVs: humans, swine, canines, equines, and various avian species, including common domestic poultry species and wild bird species. We expect to identify structural determinants for receptor binding with human-, swine-, canine-, and avian-origin IAVs. Such knowledge will help us understand the factors that contribute to influenza infection and transmission and thereby facilitate development of an effective influenza vaccine to prevent virus infection and block virus transmission. This knowledge will also help us develop rapid assays for monitoring emerging influenza threats at the animal–human interface. We also expect to develop a computational method for identifying glycan motifs associated with influenza host tropisms; this method will be able to be adapted to determine functional glycan motifs for other proteins, lectins, antibodies, antisera, and microorganisms, including those of other infectious pathogens, by using glycan arrays.

项目总结