Therapeutic Interventions Against ANDV Induced Pathogenesis
针对 ANDV 诱发发病机制的治疗干预
基本信息
- 批准号:8581639
- 负责人:
- 金额:$ 44.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-12-01 至 2016-11-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAcuteAdherens JunctionAltitudeAndes VirusAngiopoietin-1Animal ModelBlocking AntibodiesBlood VesselsBlood capillariesCapillary PermeabilityCellsClinical TrialsCytolysisCytoskeletonDasatinibDiseaseDissociationEdemaEndothelial Cell InhibitorEndothelial CellsEndotheliumEquilibriumExtravasationFDA approvedFigs - dietaryGoalsHantavirusHantavirus Pulmonary SyndromeHumanHyperbaric OxygenationHypoxiaIn VitroInfectionJointsLiquid substanceLungMediatingMesocricetus auratusModelingOnset of illnessPathogenesisPatientsPeptidesPermeabilityPharmaceutical PreparationsPhosphorylationPublishingPulmonary EdemaReceptor SignalingResearch PersonnelRespiratory InsufficiencySignal PathwaySignal TransductionSignaling ProteinSymptomsTNF geneTherapeuticTherapeutic InterventionVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth FactorsVascular PermeabilitiesVirus Diseasesanalogautocrinecadherin 5capillarycapillary bedcellular targetinginhibitor/antagonistkinase inhibitorlung hypoxiamigrastatinmortalityparacrinepreventreceptorresponsesphingosine 1-phosphatesrc-Family Kinasestranslational study
项目摘要
DESCRIPTION (provided by applicant): Hantaviruses predominantly infect endothelial cells (ECs), and in the absence of cell lysis, cause diseases associated with dramatic increases in vascular permeability. Andes virus (ANDV) infection results in acute pulmonary edema and respiratory insufficiency termed hantavirus pulmonary syndrome (HPS). Vast pulmonary capillary beds provide an abundance of ECs for ANDV to infect and infection of ECs provides a primary means for ANDV to increase capillary permeability and cause edema. ANDV infection dramatically enhances EC permeability in response to VEGF and this is not observed following infection by non-pathogenic TULV or in response to TNF1. Our recent findings indicate that ANDV infection of ECs results in the hyperphosphorylation of VEGFR2, increased dissociation of VE-cadherin from AJs and increased paracellular permeability. We have also shown that ANDV induced permeability is inhibited by angiopoietin-1 (Ang-1), or sphingosine-1 phosphate (S1P) which antagonize VEGF directed permeability. These findings suggest that ANDV induced edema may be blocked by inhibiting VEGFR2 signaling pathways. ANDV infection of Syrian hamsters is the only animal model of hantavirus disease which closely mimics HPS, resulting in fatal acute pulmonary edema. This model permits the study of potential therapeutic compounds against ANDV disease and was developed by Jay Hooper the co- investigator on this proposal. In this joint proposal with Jay Hooper, we propose to apply our basic understanding of ANDV induced EC permeability to the Syrian Hamster model of hantavirus disease. Here we will evaluate the efficacy of compounds that enhance EC barrier functions for their ability to prevent HPS-like disease in Syrian hamsters.
描述(由申请人提供):汉坦病毒主要感染内皮细胞(EC),在没有细胞裂解的情况下,引起与血管通透性显著增加相关的疾病。安第斯山脉病毒(ANDV)感染导致急性肺水肿和呼吸功能不全,称为汉坦病毒肺综合征(HPS)。巨大的肺毛细血管床为ANDV感染提供了丰富的EC,并且EC的感染为ANDV增加毛细血管通透性和引起水肿提供了主要手段。ANDV感染响应于VEGF显著增强EC渗透性,并且在非致病性TULV感染或响应于TNF 1后未观察到这一点。我们最近的研究结果表明,ANDV感染的EC的结果在VEGFR 2的过度磷酸化,增加的VE-钙粘蛋白从AJs的解离和增加的细胞旁通透性。我们还表明ANDV诱导的渗透性被血管生成素-1(Ang-1)或鞘氨醇-1磷酸(S1 P)抑制,其拮抗VEGF指导的渗透性。这些发现表明ANDV诱导的水肿可能通过抑制VEGFR 2信号通路而被阻断。ANDV感染的叙利亚仓鼠是汉坦病毒病的唯一动物模型,它与HPS非常相似,导致致命的急性肺水肿。该模型允许研究针对ANDV疾病的潜在治疗化合物,并且由JayHooper开发,JayHooper是该提议的共同研究者。在与Jay Hooper的联合提案中,我们建议将我们对ANDV诱导EC渗透性的基本理解应用于汉坦病毒病的叙利亚模型。在这里,我们将评估增强EC屏障功能的化合物在叙利亚仓鼠中预防HPS样疾病的能力的功效。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Erich R Mackow其他文献
Erich R Mackow的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Erich R Mackow', 18)}}的其他基金
Defining ANDV Virulence and Attenuation Mechanisms
定义 ANDV 毒力和减毒机制
- 批准号:
10054155 - 财政年份:2016
- 资助金额:
$ 44.57万 - 项目类别:
Dengue Infected Endothelial Cells Enhance Immune Cell Activation
登革热感染的内皮细胞增强免疫细胞激活
- 批准号:
8385024 - 财政年份:2012
- 资助金额:
$ 44.57万 - 项目类别:
Dengue Infected Endothelial Cells Enhance Immune Cell Activation
登革热感染的内皮细胞增强免疫细胞激活
- 批准号:
8495920 - 财政年份:2012
- 资助金额:
$ 44.57万 - 项目类别:
ANDV Induced Responses of Hypoxic Endothelial Cells
ANDV 诱导缺氧内皮细胞的反应
- 批准号:
8190126 - 财政年份:2011
- 资助金额:
$ 44.57万 - 项目类别:
Therapeutic Interventions Against ANDV Induced Pathogenesis
针对 ANDV 诱发发病机制的治疗干预
- 批准号:
8385518 - 财政年份:2011
- 资助金额:
$ 44.57万 - 项目类别:
ANDV Induced Responses of Hypoxic Endothelial Cells
ANDV 诱导缺氧内皮细胞的反应
- 批准号:
8264741 - 财政年份:2011
- 资助金额:
$ 44.57万 - 项目类别:
Therapeutic Interventions Against ANDV Induced Pathogenesis
针对 ANDV 诱发发病机制的治疗干预
- 批准号:
8237655 - 财政年份:2011
- 资助金额:
$ 44.57万 - 项目类别:
Determinants of Pathogenic Hantavirus Attachment
致病性汉坦病毒附着的决定因素
- 批准号:
7860323 - 财政年份:2009
- 资助金额:
$ 44.57万 - 项目类别:
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 44.57万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 44.57万 - 项目类别:
Operating Grants