RSV-induced inflammation in the brain
RSV 诱发的大脑炎症
基本信息
- 批准号:10252048
- 负责人:
- 金额:$ 19.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-02 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:1 year old2 year oldAcuteAddressAffectAgeAlveolitisAnimalsAntibodiesAstrocytesBehaviorBehavioralBlood - brain barrier anatomyBrainBronchiolitisCellsCentral Nervous System DiseasesCentral Sleep ApneaCerebrospinal FluidCessation of lifeChildClinicalCognitionCognitiveCommunitiesControl AnimalDataDeglutitionDevelopmentDiseaseDisease OutbreaksEmergency department visitEncephalopathiesExhibitsGenetic MaterialsGoalsGrantHospitalizationHumanImmune responseImmunologic MemoryImpaired cognitionInfantInfectionInfectious AgentInfiltrationInflammationInflammatoryInflammatory ResponseIntensive Care UnitsKineticsKnowledgeLearningLethargiesLower Respiratory Tract InfectionLungLung diseasesLung infectionsMolecularMusMuscleNerve TissueNeurologicNeurologic SymptomsNeuronsOtitis MediaOutpatientsPathologic ProcessesPatientsPlayPneumoniaPneumovirusPopulationPrivate PracticePublic HealthRattusRecurrenceReporterReportingResolutionRespirationRespiratory Syncytial Virus InfectionsRespiratory syncytial virusRhinitisRoleSeasonsStrabismusStructureTestingViralViremiaVirusVirus DiseasesVisitWorld Health Organizationbasebehavioral impairmentblood-brain barrier permeabilizationbrain cellbrain tissuecognitive processcytokinedesignepidemiology studyexperimental studyfeedinginsightinterestlearned behaviorlung injurymouse modelnervous system infectionneuropathologypreventrecruitsymptomatologytoolvirus genetics
项目摘要
ABSTRACT
Respiratory syncytial virus (RSV) is a highly contagious pneumovirus that infects over 70% of children under
one year of age and nearly 100% of children by age two. Due to the poor immunological memory generated
after disease resolution, RSV produces recurrent outbreaks of infection that contribute to viral dissemination in
the community. RSV produces various clinical manifestations, ranging from rhinitis and otitis media, to more
severe diseases such as pneumonia and bronchiolitis. In addition to the respiratory disease caused by RSV,
clinical reports have described the development of neurological symptoms in around 2% of RSV-infected
children. Since most children get infected by RSV every year, this fraction of the infected population can
represent a significant number of patients. Neurological symptoms include non-febrile seizures, central apnea,
lethargy, feeding/swallowing difficulties, muscular tone abnormalities, strabismus, cerebrospinal fluid (CSF)
alterations and encephalopathy. Supporting these observations, similar results have been obtained using the
murine model of RSV infection including the demonstration that RSV causes viremia and infection of the
nervous system (CNS). Strikingly, RSV infected mice and rats show both learning and behavioral alterations
after one month of infection. We have described that mice infected by RSV have altered blood brain barrier
(BBB) permeability, exhibit increased infiltration of inflammatory cells in the brain and CNS cells, such as
astrocytes, are actively infected by RSV. Considering the burden of RSV-infection in children, such a finding is
of high interest for public health. However, the pathophysiological mechanisms responsible for RSV
dissemination into the CNS and the cognitive/behavioral manifestations remain unknown. We believe that the
type of inflammatory response triggered by RSV infection in the lungs favors the development of the CNS
alterations. Our studies suggest that RSV is able to infect the CNS and promote cognitive/behavioral
impairment due to the alteration of the blood brain barrier (BBB) permeability. Thus, the opening of the BBB
could allow RSV and/or the inflammatory cells to infiltrate the brain. Based on these observations, our central
hypothesis is that the inflammatory response elicited by RSV infection leads to neurological alterations caused
by increased permeability of the BBB, the recruitment of inflammatory cells to the CNS and the infection of
nerve cells. The specific aims of this grant will address the pathological processes of RSV infection and its
effects on the CNS. This will be achieved by determining the structural and functional changes at the BBB
following RSV infection and identifying the brain cells that are infected by RSV, as well as its infection kinetics
in mice. The results obtained in this proposal will provide a better understanding of the neuropathology caused
by RSV and the possible detrimental effects at the CNS in humans. Moreover, the knowledge of the
modulation of the mechanism of RSV brain infection and its host inflammatory response could generate new
tools that can help to prevent the consequences of RSV infection over the CNS.
摘要
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Steven M Varga其他文献
Steven M Varga的其他文献
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{{ truncateString('Steven M Varga', 18)}}的其他基金
Deciphering the complexities of inflammasome activation following RSV infection
破译 RSV 感染后炎症小体激活的复杂性
- 批准号:
10655297 - 财政年份:2022
- 资助金额:
$ 19.31万 - 项目类别:
Deciphering the complexities of inflammasome activation following RSV infection
破译 RSV 感染后炎症小体激活的复杂性
- 批准号:
10388682 - 财政年份:2022
- 资助金额:
$ 19.31万 - 项目类别:
Deciphering the complexities of inflammasome activation following RSV infection
破译 RSV 感染后炎症小体激活的复杂性
- 批准号:
10807884 - 财政年份:2022
- 资助金额:
$ 19.31万 - 项目类别:
Balancing protection versus immunopathology by RSV-specific memory CD8 T cells
RSV 特异性记忆 CD8 T 细胞平衡保护与免疫病理学
- 批准号:
9977905 - 财政年份:2017
- 资助金额:
$ 19.31万 - 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
- 批准号:
7895292 - 财政年份:2009
- 资助金额:
$ 19.31万 - 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
- 批准号:
7568970 - 财政年份:2007
- 资助金额:
$ 19.31万 - 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
- 批准号:
8013503 - 财政年份:2007
- 资助金额:
$ 19.31万 - 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
- 批准号:
7758806 - 财政年份:2007
- 资助金额:
$ 19.31万 - 项目类别:
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