Gastroenteritis virus infections in South African children: secretor status-linkedsusceptibility, prevalence and genetic diversity and humoral responses to norovirusinfection

南非儿童胃肠炎病毒感染：分泌者状态相关的易感性、患病率和遗传多样性以及对诺如病毒感染的体液反应

• 批准号: 10666007
• 负责人: Janet Mans
• 金额: $ 13.7万
• 依托单位: UNIVERSITY OF PRETORIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-17 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666007
• 关键词: 2 year old; 5 year old; Adenoviruses; Age; Antibodies; Antibody Response; Astrovirus; Avidity; Binding; Biological Assay; Birth; Blocking Antibodies; Blood; Blood Group Antigens; Blood specimen; Capsid Proteins; Characteristics; Child; Chimeric Proteins; Circulation; Classification; Clinical; Communities; Complement; Data; Diagnostic; Diarrhea; Dideoxy Chain Termination DNA Sequencing; Disease; Dryness; Enteral; Environment; Exposure to; Gastroenteritis; Genetic Variation; Genome; Genomic Segment; Genotype; HIV; Hospitalization; Hospitalized Child; Human immunodeficiency virus test; Immune response; Immunoprecipitation; Infection; Laboratories; Life; Link; Luciferases; Maternal antibody; Metagenomics; Monitor; Norovirus; Pattern; Plants; Predisposition; Prevalence; Protein Microarray Assay; Protein Microchips; Province; Reverse Transcriptase Polymerase Chain Reaction; Rotavirus; Sapovirus; Secretor blood group alpha-2-fucosyltransferase; Sentinel; Seroepidemiologic Studies; Seroprevalences; Signal Transduction; South Africa; South African; Specimen; Spottings; Testing; Time; Variant; Viral Gastroenteritis; Virus; Virus Diseases; Whole Blood; age group; antibody detection; experimental study; next generation sequencing; response; viral detection; virology; virome; wastewater samples; wastewater surveillance

Abstract Norovirus, rotavirus and adenovirus are the major causes of severe viral gastroenteritis in children worldwide. This project aims to monitor the prevalence, genetic diversity, predominant and emerging strains of these viruses in South Africa (SA) over a 5-year period. In addition, the project will investigate the humoral response to norovirus infections and determine to which norovirus genotypes children in SA are exposed to in the first two years of life, and when protective antibodies are generated. We will perform parallel gastroenteritis virus surveillance 1) in children (<5 years of age) hospitalised with gastroenteritis, and 2) in wastewater influent from 11 sentinel wastewater treatment plants across SA. Complete genomes of the predominant norovirus, rotavirus and adenovirus genotypes will be determined by next generation sequencing to study the global emergence and diversification of these viruses. A protein microarray approach will be used to evaluate antibodies to a range of norovirus genotypes in children in SA. Dried blood spot specimens from HIV exposed children that were submitted for HIV testing, will be accessed once HIV testing is complete. Children will be classified in five age groups between birth and 2 years of age. Initially we will characterise the immune response against 20 norovirus strains which circulated in hospitalised children and in the environment in the recent past. The range of norovirus genotypes will be expanded during the project to reflect the current strains detected in clinical and environmental surveillance. In addition, the fucosyltransferase 2 (FUT2) secretor status (which is linked to norovirus and rotavirus susceptibility) will be determined in an effort to better understand the link between secretor status and infection with various norovirus and rotavirus genotypes. Finally, the functionality of the detected antibodies will be evaluated in terms of their avidity and ability to block binding between the norovirus major capsid protein (VP1) and histo-blood group antigens. A luciferase-VP1 fusion protein immunoprecipitation assay will be used to detect genotype-specific blocking antibodies. Seroprevalence and antibody characteristics will be compared between the five age groups 0-1 month (maternal antibodies), 2- 6 months (maternal antibodies), 7-12 months, 13-18 months and 19-24 months. This project should generate valuable data to better understand the diversity of norovirus infections and the immune response to these infections in young children. The combination of seroprevalence results with clinical and environmental data collected during the same time period will provide valuable information on the importance of the environmental strains in norovirus exposure in young children.

摘要