Do they or don't they: astrovirus-induced diarrhea

是还是不是：星状病毒引起的腹泻

• 批准号: 9804141
• 负责人: Stacey L Schultz-Cherry
• 金额: $ 8.98万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-08 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9804141
• 关键词: Age; Astrovirus; Behavior; Biological; Biology; Characteristics; Clinical; Data; Diagnosis; Diagnostic tests; Diarrhea; Disease; Elderly; Encephalitis; Epidemiology; Epithelial; Genbank; Genomics; Genotype; Goals; Gold; Heterogeneity; Human; Immunocompromised Host; In Vitro; Infection; Kinetics; Knowledge; Laboratories; Link; Longitudinal Studies; Mediating; Meningitis; Metadata; Patients; Pediatric Oncology; Pediatric cohort; Permeability; Phenotype; Public Health; Research Personnel; Role; Sex Bias; Systemic disease; Testing; Time; Viral; Viral Load result; Virus; Work; boys; co-infection; cohort; diagnostic assay; diarrheal disease; enteric infection; girls; high risk; high risk population; infection risk; male; novel; novel diagnostics; pathogen; recombinant virus; sex; virology; virome; whole genome

OVERALL ABSTRACT Human astroviruses (HAstV) are a leading cause of infectious diarrhea. Yet, the current “gold-standard” diagnostic test fails to detect 2/3 of the HAstV genotypes associated with human infection making it likely that HAstV infection is not only under-diagnosed, but more prevalent than appreciated. There has also been an increased appreciation that HAstV disease can range from asymptomatic to significant and even fatal systemic diseases beyond diarrhea including encephalitis and meningitis, particularly in high-risk populations suggesting that astrovirus-associated diarrheal disease is also not as straight-forward as dogma would have us believe. Yet, the role for distinct HAstV genotypes in disease is currently unknown and no studies to date have defined the host or viral factors connected with astroviral-associated diarrheal disease. Our proposed studies begin to fill this gap in knowledge by being the first work aimed at understanding HAstV-associated diarrhea: from epidemiology to basic virology. Strong preliminary studies suggest that diverse viral genotypes co-circulate in pediatric oncology patients with boys being four times more likely to be infected than girls, and that viruses isolated from patients have distinct in vitro phenotypes. Thus, the overall goals of our planned studies are to begin to understand HAstV-associated diarrhea in a novel high-risk population. Our central hypothesis is that the ability of astroviruses to cause diarrheal illness is largely mediated by their broad heterogeneity and distinct biological behaviors. To test our central hypothesis, we have proposed the following three interconnected but independent specific aims: 1. Understand the association between astrovirus infection and diarrheal disease. 2. Determine if diarrheal disease correlates with in vitro phenotypes. 3. Are there additional HAstV genotypes? We are uniquely suited to undertake this work given our expertise in astrovirus biology as well as having novel cohorts of pediatric oncology patients that are among the highest risk for having astrovirus infections with access to extensive metadata including onset/presence of diarrheal disease. Importantly, we have already demonstrated that our cohorts are infected with genotypes from all 3 clades, and now we will be able to determine their association with diarrheal disease. Intriguingly, there appears to be a sex bias with males more likely to be HAstV-positive. Extensive new genomic information will be generated that will be invaluable to many investigators. In the long term, these studies may reveal critical new information on the public health impact of viral enteric infections.

总体抽象 人星座病毒（HASTV）是传染性腹泻的主要原因。但是，目前的“金标准” 诊断测试无法检测到与人类感染相关的HASTV基因型的2/3 HASTV感染不仅诊断不足，而且比欣赏更普遍。也有一个 HASTV疾病可能从不对称到重大甚至致命的全身性范围内的增强欣赏 腹泻以外的疾病包括脑炎和脑膜炎，特别是在高风险人群中 表明与甲状腺病毒相关的腹泻病也不像教条那样直率 相信。然而，目前尚不清楚不同的HASTV基因型在疾病中的作用，迄今为止尚无研究 定义了与星座相关腹泻病有关的宿主或病毒因子。 我们提出的研究开始通过成为旨在理解的第一项工作来填补知识的差距 与HASTV相关的腹泻：从流行病学到基本病毒学。强有力的初步研究表明 在儿科肿瘤学患者中共同循环的潜水病毒基因型，男孩的可能性是四倍 比女孩感染了，从患者中分离出的病毒具有不同的体外表型。那，总体 我们计划的研究的目标是开始在一种新型的高风险中理解与HAST相关的腹泻 人口。我们的核心假设是，甲状腺病毒引起腹泻病的能力在很大程度上是 由它们的广泛异质性和独特的生物学行为介导。为了检验我们的中心假设，我们有 提出了以下三个相互联系但独立的特定目的： 1。了解星形病毒感染与腹泻病之间的关联。 2。确定腹泻病是否与体外表型相关。 3。还有其他HASTV基因型吗？ 我们非常适合从事这项工作，鉴于我们在星座病毒生物学方面的专业知识以及新颖 小儿肿瘤患者的同类患者是患有星形毒病毒感染的最高风险 进入广泛的元数据，包括发作/存在腹泻病。重要的是，我们已经 证明我们的队列都被所有3个进化枝的基因型感染，现在我们将能够 确定它们与腹泻病的关联。有趣的是，男性似乎有更多的性偏见 可能是HASTV阳性的。将生成广泛的新基因组信息，这对于 许多调查员。从长远来看，这些研究可能会揭示有关公共卫生的关键新信息 病毒启动子的影响。