AIDS-related HSV-1 retinal necrosis: Innate immunity and virus spread
艾滋病相关的 HSV-1 视网膜坏死:先天免疫和病毒传播
基本信息
- 批准号:10328549
- 负责人:
- 金额:$ 23.4万
- 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:2021-02-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS dementiaAcquired Immunodeficiency SyndromeAcuteAcute Retinal Necrosis SyndromeAddressAnimal ModelBiological AssayBrainClinicalDNADevelopmentDiagnostic testsEncephalitisEvolutionEyeGoalsHIVHerpes encephalitisHerpesvirus 1Immunocompromised HostImmunosuppressionIncidenceInfectionInvestigationJC VirusLeadMediatingMessenger RNAMethodsMissionModelingMusNatural ImmunityNecrosisNeural PathwaysOptic NervePatientsPatternPerformancePeripheralPlaque AssayPrincipal InvestigatorProgressive Multifocal LeukoencephalopathyPublic HealthRIPK3 geneRetinaRetinal DiseasesRetroviridaeReverse Transcriptase Polymerase Chain ReactionRoleSignal PathwaySiteTestingTimeTissuesTransactivationTravelUnited States National Institutes of HealthVariantVirusVirus DiseasesVirus ReplicationWestern Blottingacute symptomantiretroviral therapybrain parenchymabrain tissuechemokineclinically relevantcytokinemacrophagemouse developmentnano-stringnervous system disordernovelnovel therapeutic interventionpreventprogramsseropositivevirus-induced neurologic disease
项目摘要
Program Director/Principal Investigator (Last, First, Middle): Dix, Richard D
Project Summary
AIDS patients can develop a variant of acute retinal necrosis (ARN) designated progressive outer retinal
necrosis (PORN) caused by herpes simplex virus type 1 (HSV-1). Although infectious virus is present within
retinal tissues during PORN, AIDS patients fail to develop acute herpes simplex encephalitis (HSE) suggesting
virus is either contained within retinal tissues or indeed spreads to the brain but is contained within neural
pathways to cause subclinical HSV-1 encephalitis. A critical barrier to progress in advancing our
understanding of HSV-1 retinal necrosis vis-à-vis HSE during AIDS has been the lack of a clinically relevant
animal model for AIDS-related HSV-1 retinal necrosis. The proposed project will address this critical barrier to
progress by using a newly developed and clinically relevant animal model of HSV-1-induced retinal disease in
mice with retrovirus-induced immunosuppression (MAIDS) that histopathologically mimics PORN in AIDS
patients. The goal of this project is to address the problem of AIDS-related HSV-1 PORN and HSE and the
critical barrier to progress by obtaining the information needed to understand the role of innate immunity in
halting virus spread from retina to brain or minimizing virus spread within the brain to cause subclinical
encephalitis using our novel MAIDS-model of HSV-1 PORN. Our central hypothesis is that one or more
components of innate immunity that operate during retrovirus-induced immunosuppression prevent onset of
acute HSE by either blocking HSV-1 spread to the brain or containing HSV-1 replication within the brain to
produce subclinical encephalitis. Our objectives are to use our novel MAIDS model of HSV-1 PORN to (1)
define with certainty the fate of HSV-1 infection within retinal tissues and the extent (if any) of virus spread to
brain tissues, and (2) begin to understand the contributions of key components of innate immunity in containing
HSV-1 infection at the retina and/or within the brain to yield a subclinical encephalitis. These objectives will be
met through successful completion of two Specific Aims: (1) determine the extent of virus spread in mice with
MAIDS-related HSV-1 PORN and (2) determine the relative roles of key components of innate immunity in
containing virus spread in mice with MAIDS-related HSV-1 PORN. The impact on the field of AIDS will include
(1) the heretofore unrecognized role of innate immunity to contain HSV-1 spread from retina to brain and/or
within the brain parenchyma during retrovirus-induced immunosuppression and (2) perhaps the heretofore
unrecognized potential development of subclinical HSE in HIV-immunosuppressed patients.
PHS 398/2590 (Rev. 06/09) Page Continuation Format Page
项目主管/首席研究员(最后、第一、中):Dix, Richard D
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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Richard D Dix其他文献
Richard D Dix的其他文献
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{{ truncateString('Richard D Dix', 18)}}的其他基金
Programmed cell death and cytomegalovirus retinitis pathogenesis
程序性细胞死亡和巨细胞病毒性视网膜炎发病机制
- 批准号:
10655133 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Cytomegalovirus retinitis pathogenesis: Mechanisms of retinal tissue destruction
巨细胞病毒视网膜炎发病机制:视网膜组织破坏机制
- 批准号:
9070590 - 财政年份:2015
- 资助金额:
$ 23.4万 - 项目类别:
Cytomegalovirus retinitis pathogenesis: Mechanisms of retinal tissue destruction
巨细胞病毒性视网膜炎发病机制:视网膜组织破坏机制
- 批准号:
8886844 - 财政年份:2015
- 资助金额:
$ 23.4万 - 项目类别:
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