Innate Immunity & Hemorrhagic Fever Viruses
Innate Immunity & Hemorrhagic Fever Viruses
批准号:
7645348
负责人:
Robert William Finberg
金额:
$68.16万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-03-01 至 2009-02-28
关键词:
AcuteAffectAntigen PresentationArenavirusB-LymphocytesBiologyBioterrorismBlood ProteinsCD14 geneCell LineCellsCessation of lifeChemicalsCollaborationsDataDevelopmentDiseaseDoseEbola virusEngineeringEventFeverFilovirusFunctional disorderGlycoproteinsHumanHuman Cell LineHypotensionIL8 geneImmune responseImmune systemImmunityIn VitroIndividualInfectionInflammatoryInflammatory Response PathwayKnockout MiceLeadLeukopeniaLymphocytic choriomeningitis virusMediatingMeningitisMorbidity - disease rateMusNatural ImmunityPathogenesisPattern RecognitionPattern recognition receptorPhasePreclinical Drug EvaluationProductionProteinsRateReporterRoleRunningScreening procedureSepsisSeriesShockSignal Transduction PathwayT-LymphocyteTLR1 geneTLR3 geneTLR4 geneTLR6 geneTestingTherapeuticThrombocytopeniaToll-Like Receptor 2Toll-like receptorsVaccinesVariantViral Hemorrhagic FeversViral ProteinsVirusVirus DiseasesWorkacquired immunitycytokinehemorrhagic fever virusin vivomacrophagemortalitynovelnovel therapeuticsreceptorresearch studyresponsesmall moleculesmall molecule libraries
中文摘要
这个项目将研究先天免疫系统在病毒感染的病理生理学中的作用。
出血热将研究两种可能成为生物恐怖主义的病毒:1)埃博拉病毒,
丝状病毒,其引起以发热、白细胞减少、休克和死亡为特征的急性疾病,和2)
淋巴细胞性脉络丛脑膜炎病毒LCMV是一种沙粒病毒,其引起的疾病特征为:
小鼠的白细胞减少症和血小板减少症以及人类的脑膜炎。与之相关的高死亡率
埃博拉病毒感染已被证明与病毒感染后发生的细胞因子释放直接相关。
巨噬细胞感染。埃博拉病毒诱导这种细胞因子反应的机制将被定义,
将筛选化合物抑制该活性的能力。初步数据显示,
Toll样受体2(TLR-2)和CD 14在对LCMV的细胞因子应答中的作用。TLR-2和CD 14是
识别蛋白,其在细菌性脓毒症中的作用最近已被确定。两者都与
对病毒的免疫反应。使用转染的细胞系和可用的敲除小鼠,
这些蛋白质影响细胞因子的初始诱导以及随后的
将定义对LCMV和埃博拉病毒的免疫应答。特定的TLR(和其他“模式
识别蛋白(“识别蛋白”)参与这些反应以及它们的相互作用将被研究。的影响
将研究这些早期识别事件对长期带状T细胞免疫的影响。这些研究将
导致更好地理解先天免疫系统在介导免疫应答中的作用。
出血热病毒的病理生理学,并应导致新的治疗方法,这些
疾病
英文摘要
This project will examine the role of the innate immune system in the pathophysiology of the viral
hemorrhagic fevers. Two viruses which are potential agents of bioterrorism, will be studied: 1) Ebola virus, a
filovirus, which induces an acute illness characterized by fever, leucopenia, shock, and death, and 2)
Lymphocytic Choriomeningitis Virus LCMV an arenavirus which causes an illness characterized by
leucopenia and thrombocytopenia in mice and meningitis in humans. The high mortality rate associated with
Ebola infection has-been demonstrated to be directly associated with cytokine release which occurs after viral
infection of macrophages. The mechanism by which Ebola induces this cytokine response will be defined and
compounds will be screened for their ability to inhibit this activity. Preliminary data indicate a major role for
Toll Like Receptor 2 (TLR-2) and CD14 in the cytokine response to LCMV. TLR-2 and CD14 are pattern
recognition proteins whose role in bacterial sepsis has been recently defined. Both have also been associated
with the immune responses to viruses. Using transfected cell lines and available knockout mice the
mechanism by which these proteins affect both initial induction of cytokines as well as the subsequent
immune responses to LCMV and Ebola virus will be defined. The specific TLRs (and other "pattern
recognition proteins") involved in these responses as well as their interactions will be studied. The effect of
these early recognition events on long-term Band T cell immunity will be investigated. These studies will
result in a better understanding of the role that the innate immune system has in mediating the
pathophysiology of hemorrhagic fever viruses and should lead to new therapeutic approaches to these
diseases.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
International Immunocompromised Host Society's 19th International Symposium on Infections in the Immunocompromised Host
-
批准号:9260163
-
项目类别:
-
资助金额:$0.6万
-
财政年份:2016
-
负责人:Robert William Finberg
-
依托单位:
18th International Symposium on Infections in the Immunocompromised Host
-
批准号:8720337
-
项目类别:
-
资助金额:$0.8万
-
财政年份:2014
-
负责人:Robert William Finberg
-
依托单位:
17th International Symposium on Infections in the Immunocompromised Host
-
批准号:8330069
-
项目类别:
-
资助金额:$0.8万
-
财政年份:2012
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity Hemorrhagic fever viruses
-
批准号:8233435
-
项目类别:
-
资助金额:$46.31万
-
财政年份:2011
-
负责人:Robert William Finberg
-
依托单位:
Toll2011 Meeting, Decoding Innate Immunity
-
批准号:8130053
-
项目类别:
-
资助金额:$1.2万
-
财政年份:2011
-
负责人:Robert William Finberg
-
依托单位:
16th Symposium on Infections in the Immunocompromised Host
-
批准号:7994945
-
项目类别:
-
资助金额:$0.43万
-
财政年份:2010
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity Hemorrhagic fever viruses
-
批准号:7669766
-
项目类别:
-
资助金额:$43.74万
-
财政年份:2009
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Pathogensis
-
批准号:7877330
-
项目类别:
-
资助金额:$2.07万
-
财政年份:2009
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Infection
-
批准号:7914345
-
项目类别:
-
资助金额:$182.82万
-
财政年份:2009
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Infection
-
批准号:7695247
-
项目类别:
-
资助金额:$185.64万
-
财政年份:2009
-
负责人:Robert William Finberg
-
依托单位:
Pathogenesis of myocarditis
-
批准号:7229933
-
项目类别:
-
资助金额:$19.72万
-
财政年份:2006
-
负责人:Robert William Finberg
-
依托单位:
Pathogenesis of myocarditis
-
批准号:7030183
-
项目类别:
-
资助金额:$24.34万
-
财政年份:2006
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Pathogenesis
-
批准号:7389553
-
项目类别:
-
资助金额:$30.52万
-
财政年份:2005
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Pathogenesis
-
批准号:7578327
-
项目类别:
-
资助金额:$30.52万
-
财政年份:2005
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Pathogenesis
-
批准号:7190470
-
项目类别:
-
资助金额:$31.11万
-
财政年份:2005
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Pathogensis
-
批准号:7025825
-
项目类别:
-
资助金额:$32.02万
-
财政年份:2005
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and Herpes Simplex Pathogenesis
-
批准号:6903196
-
项目类别:
-
资助金额:$35.85万
-
财政年份:2005
-
负责人:Robert William Finberg
-
依托单位:
Cellular Immunity to Category A-C Viruses in Humans
-
批准号:8243671
-
项目类别:
-
资助金额:$314.38万
-
财政年份:2003
-
负责人:Robert William Finberg
-
依托单位:
Cellular Immunity to Category A-C Viruses in Humans
-
批准号:8452136
-
项目类别:
-
资助金额:$295.52万
-
财政年份:2003
-
负责人:Robert William Finberg
-
依托单位:
Innate Immunity and LCMV
-
批准号:6711613
-
项目类别:
-
资助金额:$35.66万
-
财政年份:2003
-
负责人:Robert William Finberg
-
依托单位:
海外基金