T-cell immunity to polyomavirus infection
T细胞对多瘤病毒感染的免疫
基本信息
- 批准号:8687581
- 负责人:
- 金额:$ 38.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-23 至 2016-06-30
- 项目状态:已结题
- 来源:
- 关键词:AIDS/HIV problemAcuteAffinityAgingAnimalsAntigensAntiviral AgentsAntiviral TherapyAutoimmune ProcessBK VirusBindingCD4 Positive T LymphocytesCD8B1 geneCell Cycle KineticsCellsCrohn&aposs diseaseCutaneousDataDefectDemyelinating DiseasesDepressed moodDisabled PersonsDiseaseDysplasiaEpitopesEvolutionFlow CytometryFunctional disorderFundingGene ChipsGene SilencingGenerationsGenesGeneticGenomeGoalsHIV-1HerpesviridaeHumanImmuneImmunityImmunocompetentImmunosuppressionImmunotherapyIndividualInfectionInflammationInflammatoryJC VirusKidney DiseasesKidney TransplantationKineticsLifeLigandsLymphoidMHC binding peptideMalignant NeoplasmsMediatingMemoryMerkel cell carcinomaModelingMolecularMultiple SclerosisMusNatural ImmunityOrganOutputPathogenesisPatientsPeptide/MHC ComplexPolyomaviridaePolyomavirusPolyomavirus InfectionsPopulationProgressive Multifocal LeukoencephalopathyProteinsPsoriasisRecruitment ActivityResearchResistanceRespiratory Tract InfectionsSecondary toSignal TransductionSkinSpecies SpecificityStagingSystemT cell differentiationT cell responseT memory cellT-LymphocyteTechnologyTestingTransgenic MiceTransgenic OrganismsTropismVariantVertebratesViral AntigensVirusVirus DiseasesWestern Blottingadaptive immunityeffective therapyhandicapping conditioninnovationkidney allograftlytic replicationmortalitymouse polyomavirusmutantnovelparent grantpathogenresidenceresponseretroviral transductionself-renewaltherapy developmenttraffickingtumortumorigenesisvirome
项目摘要
DESCRIPTION (provided by applicant): The long-term goal of this renewal application is to understand the mechanisms responsible for generating and maintaining antiviral CD8 T cell responses required to contain persistent "smoldering" viral infections. Persistent virus infections
may be categorized into those that are chronically viremic (e.g., HIV-1) and those that maintain themselves by repetitive cycles of reactivation of lytic replication from a noninfectious latent state (e.g., herpesviruses). Polyomaviruses (PyV), silent residents of the "virome" of many vertebrates including humans, persist in a low-level infectious state. However, under conditions of immunosuppression human PyVs can incur life-threatening disease. BK virus is a significant cause of kidney transplant dysfunction and loss. A major cause of mortality in the HIV/AIDS population, JC virus-induced Progressive Multifocal Leukoencephalopathy (PML) has recently emerged in individuals receiving humoral immunotherapies for autoimmune and inflammatory diseases (e.g., multiple sclerosis, Crohn's disease, and severe psoriasis). Several new human PyVs have also recently been isolated from nonbacterial respiratory infections and as a likely causative agent for an aggressive fatal cutaneous malignancy. No effective therapies for PyV infection are available. Due to the tight species specificity of Polyomaviridae that restricts infection to natural animal reservoirs, we have an incomplete understanding of the immune mechanisms needed to keep these smoldering infections in check. Using mouse polyomavirus (MPyV), we discovered that na¿ve virus-specific CD8 T cells are recruited during persistent infection. Data generated in the last funding cycle reveal that temporal differences in recruitment
dramatically modulate the quality of the memory T cell compartment. We hypothesize that dynamic changes over the course of infection govern whether MPyV-specific CD8 T cells differentiate into competent memory cells, which, in turn, will be reflected at their levels of gen expression and the TCR-CD8-peptide:MHC tri-molecular interaction. Understanding the mechanisms that control the generation of durable anti-MPyV CD8 T cell memory may help in the development of interventions to enhance immunity to human PyV infections. We will test the above hypothesis in the following three Specific Aims: Aim 1: To define determinants regulating the contribution of acute vs. persistent infection-recruited antiviral CD8 T cells to the memory population. Aim 2: To determine molecular signaling mechanisms underlying the functional differences between acute and persistent infection-recruited MPyV-specific CD8 T cells. Aim 3: To define molecular differences between MPyV-specific memory T cells recruited during acute and persistent infection.
描述(由申请人提供):本次续期申请的长期目标是了解产生和维持抗病毒CD8 T细胞反应的机制,这些反应是抑制持续“阴燃”病毒感染所必需的。持续性病毒感染
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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Aron Eliot Lukacher其他文献
Aron Eliot Lukacher的其他文献
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{{ truncateString('Aron Eliot Lukacher', 18)}}的其他基金
Deciphering Early Stages of Polyomavirus CNS Pathogenesis and Immunity
破译多瘤病毒中枢神经系统发病机制和免疫的早期阶段
- 批准号:
10449608 - 财政年份:2022
- 资助金额:
$ 38.25万 - 项目类别:
Deciphering Early Stages of Polyomavirus CNS Pathogenesis and Immunity
破译多瘤病毒中枢神经系统发病机制和免疫的早期阶段
- 批准号:
10785321 - 财政年份:2022
- 资助金额:
$ 38.25万 - 项目类别:
Deciphering Early Stages of Polyomavirus CNS Pathogenesis and Immunity
破译多瘤病毒中枢神经系统发病机制和免疫的早期阶段
- 批准号:
10610484 - 财政年份:2022
- 资助金额:
$ 38.25万 - 项目类别:
Defining Early Stages of Polyomavirus CNS Pathogenesis and Immunity
定义多瘤病毒中枢神经系统发病机制和免疫的早期阶段
- 批准号:
10365345 - 财政年份:2016
- 资助金额:
$ 38.25万 - 项目类别:
Pathogenesis of Mouse Polyomavirus-associated CNS Demyelination
小鼠多瘤病毒相关中枢神经系统脱髓鞘的发病机制
- 批准号:
9185385 - 财政年份:2016
- 资助金额:
$ 38.25万 - 项目类别:
A Mouse Model to Define Immunovirologic Determinants of Polyomavirus CNS Disease
定义多瘤病毒中枢神经系统疾病免疫病毒学决定因素的小鼠模型
- 批准号:
8853962 - 财政年份:2014
- 资助金额:
$ 38.25万 - 项目类别:
A Mouse Model to Define Immunovirologic Determinants of Polyomavirus CNS Disease
定义多瘤病毒中枢神经系统疾病免疫病毒学决定因素的小鼠模型
- 批准号:
9920216 - 财政年份:2014
- 资助金额:
$ 38.25万 - 项目类别:
A Mouse Model to Define Immunovirologic Determinants of Polyomavirus CNS Disease
定义多瘤病毒中枢神经系统疾病免疫病毒学决定因素的小鼠模型
- 批准号:
9244865 - 财政年份:2014
- 资助金额:
$ 38.25万 - 项目类别:
A Mouse Model to Define Immunovirologic Determinants of Polyomavirus CNS Disease
定义多瘤病毒中枢神经系统疾病免疫病毒学决定因素的小鼠模型
- 批准号:
10133156 - 财政年份:2014
- 资助金额:
$ 38.25万 - 项目类别:
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