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.

抽象的 诺如病毒、轮状病毒和腺病毒是儿童严重病毒性胃肠炎的主要原因 全世界。该项目旨在监测患病率、遗传多样性、主要和 五年内这些病毒在南非 (SA) 出现的新毒株。此外，该项目 将研究对诺如病毒感染的体液反应并确定针对哪种诺如病毒 南澳儿童在生命的头两年接触到的基因型，以及当采取保护措施时 产生抗体。我们将对儿童进行平行胃肠炎病毒监测 1) （<5岁）因肠胃炎住院，以及2）来自11个哨点的废水进水 南澳各地的废水处理厂。主要诺如病毒的完整基因组， 轮状病毒和腺病毒基因型将通过下一代测序确定以进行研究 这些病毒在全球的出现和多样化。蛋白质微阵列方法将是 用于评估南澳儿童针对一系列诺如病毒基因型的抗体。干血斑 提交进行艾滋病毒检测的艾滋病毒暴露儿童的样本将在一次后获取 HIV 检测已完成。儿童将被分为出生至 2 岁之间的五个年龄组 的年龄。首先，我们将描述针对 20 种诺如病毒株的免疫反应，这些病毒株 最近在住院儿童和环境中传播。范围为 项目期间将扩大诺如病毒基因型，以反映目前在 临床和环境监测。此外，岩藻糖基转移酶 2 (FUT2) 分泌者 将确定状态（与诺如病毒和轮状病毒易感性相关） 更好地了解分泌者状态与各种诺如病毒感染之间的联系 轮状病毒基因型。最后，将根据以下方面评估检测到的抗体的功能 他们的亲合力和阻断诺如病毒主要衣壳蛋白（VP1）和 组织血型抗原。荧光素酶-VP1融合蛋白免疫沉淀测定将 用于检测基因型特异性阻断抗体。血清阳性率和抗体 将比较五个年龄组 0-1 个月（母体抗体）、2- 6个月（母源抗体）、7-12个月、13-18个月和19-24个月。这个项目 应产生有价值的数据，以更好地了解诺如病毒感染的多样性和 幼儿对这些感染的免疫反应。血清阳性率的组合 同一时间段内收集的临床和环境数据的结果将提供 关于环境菌株在诺如病毒暴露中的重要性的宝贵信息 年幼的孩子。