Elucidation of Pathogenic Mechanisms underlying Norovirus Diarrhea
阐明诺如病毒腹泻的致病机制
基本信息
- 批准号:10624395
- 负责人:
- 金额:$ 60.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcuteAdultAnimal ModelAttenuatedB-LymphocytesBiological AssayBiological ModelsBiologyCellsChildhoodDataDendritic CellsDiarrheaDiseaseEnsureEnteralEpithelial CellsEpitheliumEventFecesGastroenteritisGastrointestinal DiseasesGeneticGenetic DeterminismGenetic TranscriptionHumanImmuneImmune TargetingImmunocompetentImmunologicsInfectionIntestinal DiseasesIntestinesLaboratory miceLymphocyteMacrophageMapsModelingMusNeonatalNorovirusOralOutcomePathogenesisPathogenicityPathologicPeyer&aposs PatchesPredispositionPrimary InfectionProcessRNAResearchResistanceRotavirus InfectionsSeverity of illnessSmall IntestinesSymptomsSystemT-LymphocyteTestingTissuesTropismViralViral ProteinsVirulenceVirulence FactorsVirulentVirusVirus ReplicationWorkacute infectioncell typecellular targetingdiarrheal diseaseenteric infectiongastrointestinal epitheliuminnovationinsightinterdisciplinary approachintestinal epitheliummouse modelneonatal infectionneonatal miceneonateneutrophilnovelpupsecondary lymphoid organvirus geneticsvirus host interaction
项目摘要
Project Summary
Noroviruses are a major cause of acute gastroenteritis and the leading cause of severe childhood
diarrhea globally. Our discovery of murine norovirus (MNV) in 2003 accelerated progress in the
field by providing a small animal model and enabling further understanding of the pathogenesis
of these enteric viruses. Yet a major limitation of this model system is that wild-type laboratory
mice have not been shown to develop overt disease when infected with MNV, in contrast to human
norovirus which is symptomatic in immunocompetent hosts. This limits the field’s ability to
elucidate norovirus-induced events responsible for disease. It should be noted, however, that all
virulence studies of MNV performed to date have used adult mice. Considering that human
norovirus infections are more severe in younger hosts, we hypothesized that young mice would
likewise be susceptible to MNV disease. We have generated exciting data confirming that oral
MNV infection causes acute self-resolving diarrhea in neonatal pups, a transformative discovery
for the norovirus field. Gastrointestinal disease severity is regulated by viral genetic determinants
and is associated with pathological changes to the intestinal epithelium although the main targets
of infection are intestinal immune cells. We propose to use this novel system to test our working
model that infection of intestinal immune cells leads to disruption of the epithelium and
consequent diarrhea. Our main objectives are to elucidate the viral determinants of diarrhea,
define the key immune cell targets of infection, and probe the interactions of the virus with the
intestinal epithelium. The integration of these aims will enable us to map key virus-host
interactions responsible for intestinal disease.
项目摘要
诺如病毒是急性胃肠炎的主要原因,也是儿童重症的主要原因
全球腹泻我们在2003年发现了鼠诺如病毒(MNV),加速了
通过提供小动物模型和能够进一步理解发病机制,
这些肠道病毒。然而,该模型系统的一个主要限制是野生型实验室
与人相比,小鼠在感染MNV时没有显示出明显的疾病
在免疫活性宿主中有症状的诺如病毒。这限制了该领域的能力,
阐明诺如病毒诱导的事件引起的疾病。然而,应当指出,所有
迄今为止进行的MNV毒力研究使用的是成年小鼠。考虑到人类的
诺如病毒感染在年轻的宿主中更严重,我们假设年轻的小鼠会
也容易感染MNV疾病。我们已经产生了令人兴奋的数据证实,
MNV感染导致新生幼崽急性自愈性腹泻,这是一个变革性的发现
诺如病毒领域胃肠道疾病的严重程度受病毒遗传决定因素的调节
并且与肠上皮的病理变化有关,
肠道免疫细胞。我们建议使用这个新的系统来测试我们的工作
肠免疫细胞的感染导致上皮细胞破坏的模型,
随之而来的腹泻我们的主要目标是阐明腹泻的病毒决定因素,
确定感染的关键免疫细胞靶点,并探测病毒与
肠上皮这些目标的整合将使我们能够绘制出关键的病毒宿主
肠道疾病的相互作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Stephanie M Karst其他文献
Stephanie M Karst的其他文献
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{{ truncateString('Stephanie M Karst', 18)}}的其他基金
Elucidation of Pathogenic Mechanisms underlying Norovirus Diarrhea
阐明诺如病毒腹泻的致病机制
- 批准号:
10413248 - 财政年份:2021
- 资助金额:
$ 60.4万 - 项目类别:
Elucidation of Pathogenic Mechanisms underlying Norovirus Diarrhea
阐明诺如病毒腹泻的致病机制
- 批准号:
10277083 - 财政年份:2021
- 资助金额:
$ 60.4万 - 项目类别:
Suppression of Enteric Norovirus Infection by Microbiota-Regulated Bile Acids
通过微生物群调节的胆汁酸抑制肠道诺如病毒感染
- 批准号:
10061535 - 财政年份:2018
- 资助金额:
$ 60.4万 - 项目类别:
Suppression of Enteric Norovirus Infection by Microbiota-Regulated Bile Acids
通过微生物群调节的胆汁酸抑制肠道诺如病毒感染
- 批准号:
10517512 - 财政年份:2018
- 资助金额:
$ 60.4万 - 项目类别:
Suppression of Enteric Norovirus Infection by Microbiota-Regulated Bile Acids
通过微生物群调节的胆汁酸抑制肠道诺如病毒感染
- 批准号:
10289716 - 财政年份:2018
- 资助金额:
$ 60.4万 - 项目类别:
Identification of Host and Viral Determinants of Human Norovirus B cell Infection
人诺如病毒 B 细胞感染的宿主和病毒决定因素的鉴定
- 批准号:
10062847 - 财政年份:2016
- 资助金额:
$ 60.4万 - 项目类别:
Role of Intestinal Bacteria in Human Norovirus Infection
肠道细菌在人类诺如病毒感染中的作用
- 批准号:
9208092 - 财政年份:2015
- 资助金额:
$ 60.4万 - 项目类别:
Role of Intestinal Bacteria in Human Norovirus Infection
肠道细菌在人类诺如病毒感染中的作用
- 批准号:
9416071 - 财政年份:2015
- 资助金额:
$ 60.4万 - 项目类别:
Role of Intestinal Bacteria in Human Norovirus Infection
肠道细菌在人类诺如病毒感染中的作用
- 批准号:
8863018 - 财政年份:2015
- 资助金额:
$ 60.4万 - 项目类别:
Lack of protective immunity to murine norovirus infection
缺乏对鼠诺如病毒感染的保护性免疫力
- 批准号:
8263416 - 财政年份:2010
- 资助金额:
$ 60.4万 - 项目类别:
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