HIV and substances of abuse influence exosomes and endothelial cell function

HIV 和滥用物质影响外泌体和内皮细胞功能

基本信息

  • 批准号:
    9304176
  • 负责人:
  • 金额:
    $ 37.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-08-01 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): HIV infection results in CNS complications, with nearly 75% of patients with advanced HIV disease showing subclinical to clinical neurological manifestations. Additional sequelae have patients on long-term successful cART therapy who suffer from residual and end organ diseases of HIV infection. Endothelial cell dysfunction is central to HIV neuropathogenesis. A compromised blood brain barrier results in increased leukocyte transmigration, HIV infection, and the establishment of a highly inflammatory environment, which further aggravates HIV-associated neurological disease. Microvesicles are secreted from nearly every cell type. Many types exist, which we shall refer to collectively as exosomes. These circulate in the bloodstream of HIV patients. They influence intercellular communication at both local and distant sites from their cellular source. Vascular, lymphatic, and barrier endothelial cells, perhaps more than any other cell type, are constantly exposed to circulating exosomes. HIV infection can affect the composition of exosomes and utilizes these vesicles to facilitate viral pathogenesis and spread. Exosomes from infected cells can contain viral proteins, host microRNAs and proteins that trigger responses in endothelial cells, all of which can promote HIV pathogenesis. We showed this for exosomes circulating in HIV associated cancer patients and animal models (Chugh et al. PLoS Pathog. 2013;9(7):e1003484). Drugs of abuse including cocaine and cannibinoids are associated with increased HIV risk and these substances can be detrimental to HIV progression and contribute to HIV-associated neurological complications. Several studies have demonstrated that these drugs independently trigger distinct changes in endothelial cell function. However, the influence of drugs of abuse on exosome production, composition and function, especially in the context of HIV infection, represents a significant gap in our knowledge. Therefore, there is a critical need to understand the role of exosomes in HIV pathogenesis and factors that may influence HIV exosome-induced intercellular communication such as drug use. This may also lead to identification of potential therapeutic targets to block specific exosomal cargo and/or downstream effects in endothelial cells that may promote disease progression. This R01 application seeks to address how exosomes from HIV-infected cells affect blood brain barrier permeability and endothelial cell dysfunction and how drugs of abuse may influence exosomal cargo and function.


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 }}

Dirk P Dittmer其他文献

Determinants of mTOR inhibitor therapy in AIDS-associated malignancies
  • DOI:
    10.1186/1750-9378-7-s1-o9
  • 发表时间:
    2012-04-19
  • 期刊:
  • 影响因子:
    2.800
  • 作者:
    Dirk P Dittmer;Blossom Damania;Sang-Hoon Sin;Debasmita Roy
  • 通讯作者:
    Debasmita Roy
The use of high-dose azidothymidine in combination with chemotherapy upfront is an effective treatment approach for gamma-herpes virus-related non-Hodgkin’s lymphomas
  • DOI:
    10.1186/1750-9378-5-s1-a81
  • 发表时间:
    2010-10-11
  • 期刊:
  • 影响因子:
    2.800
  • 作者:
    Ulas Darda Bayraktar;Eileen Bernal;Lisa Cabral;William J Harrington;Dirk P Dittmer;Juan Carlos Ramos
  • 通讯作者:
    Juan Carlos Ramos

Dirk P Dittmer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('Dirk P Dittmer', 18)}}的其他基金

PQ6: Transgenic Mouse Model for Kaposi Sarcoma
PQ6:卡波西肉瘤转基因小鼠模型
  • 批准号:
    10334549
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
Project 2: Clinical and molecular determinants of HIV-associated Kaposi Sarcoma progression under local standard-of-care therapy in Malawi and South Africa
项目 2:马拉维和南非当地标准护理治疗下 HIV 相关卡波西肉瘤进展的临床和分子决定因素
  • 批准号:
    10434864
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
Project 2: Clinical and molecular determinants of HIV-associated Kaposi Sarcoma progression under local standard-of-care therapy in Malawi and South Africa
项目 2:马拉维和南非当地标准护理治疗下 HIV 相关卡波西肉瘤进展的临床和分子决定因素
  • 批准号:
    10652401
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
Project 2: Clinical and molecular determinants of HIV-associated Kaposi Sarcoma progression under local standard-of-care therapy in Malawi and South Africa
项目 2:马拉维和南非当地标准护理治疗下 HIV 相关卡波西肉瘤进展的临床和分子决定因素
  • 批准号:
    10084558
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
PQ6: Transgenic Mouse Model for Kaposi Sarcoma
PQ6:卡波西肉瘤转基因小鼠模型
  • 批准号:
    10579826
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
PQ6: Transgenic Mouse Model for Kaposi Sarcoma
PQ6:卡波西肉瘤转基因小鼠模型
  • 批准号:
    10115683
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
Project 2: Clinical and molecular determinants of HIV-associated Kaposi Sarcoma progression under local standard-of-care therapy in Malawi and South Africa
项目 2:马拉维和南非当地标准护理治疗下 HIV 相关卡波西肉瘤进展的临床和分子决定因素
  • 批准号:
    10238161
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
Planning for a National Non-Communicable Disease Center of Research Excellence
规划国家非传染性疾病卓越研究中心
  • 批准号:
    9337384
  • 财政年份:
    2016
  • 资助金额:
    $ 37.05万
  • 项目类别:
Planning for a National Non-Communicable Disease Center of Research Excellence
规划国家非传染性疾病卓越研究中心
  • 批准号:
    9193832
  • 财政年份:
    2016
  • 资助金额:
    $ 37.05万
  • 项目类别:
Origin and Lineage of Differentiation of Kaposi's Sarcoma
卡波西肉瘤的起源和分化谱系
  • 批准号:
    8839925
  • 财政年份:
    2015
  • 资助金额:
    $ 37.05万
  • 项目类别:

相似海外基金

RESEARCH SUPPORT SERVICES FOR THE DIVISION OF ACQUIRED IMMUNODEFICIENCY SYNDROME
获得性免疫缺陷综合症分类的研究支持服务
  • 批准号:
    10219039
  • 财政年份:
    2020
  • 资助金额:
    $ 37.05万
  • 项目类别:
RESEARCH SUPPORT SERVICES FOR THE DIVISION OF ACQUIRED IMMUNODEFICIENCY SYNDROME
获得性免疫缺陷综合症分类的研究支持服务
  • 批准号:
    9981476
  • 财政年份:
    2019
  • 资助金额:
    $ 37.05万
  • 项目类别:
IGF::OT::IGF RESEARCH SUPPORT SERVICES FOR THE DIVISION OF ACQUIRED IMMUNODEFICIENCY SYNDROME
IGF::OT::IGF 针对获得性免疫缺陷综合症分类的研究支持服务
  • 批准号:
    9364184
  • 财政年份:
    2016
  • 资助金额:
    $ 37.05万
  • 项目类别:
Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) in Saskatchewan- Where are we now and what does the future hold?
萨斯喀彻温省的人类免疫缺陷病毒(HIV)和获得性免疫缺陷综合症(艾滋病)——我们现在在哪里以及未来会怎样?
  • 批准号:
    236932
  • 财政年份:
    2011
  • 资助金额:
    $ 37.05万
  • 项目类别:
    Miscellaneous Programs
ACQUIRED IMMUNODEFICIENCY SYNDROME RESEARCH REVIEW COMMI
获得性免疫缺陷综合症研究审查委员会
  • 批准号:
    3554155
  • 财政年份:
    1991
  • 资助金额:
    $ 37.05万
  • 项目类别:
ACQUIRED IMMUNODEFICIENCY SYNDROME REVIEW
获得性免疫缺陷综合症审查
  • 批准号:
    6766860
  • 财政年份:
    1991
  • 资助金额:
    $ 37.05万
  • 项目类别:
ACQUIRED IMMUNODEFICIENCY SYNDROME RESEARCH REVIEW COMMI
获得性免疫缺陷综合症研究审查委员会
  • 批准号:
    3554156
  • 财政年份:
    1991
  • 资助金额:
    $ 37.05万
  • 项目类别:
ACQUIRED IMMUNODEFICIENCY SYNDROME REVIEW
获得性免疫缺陷综合症审查
  • 批准号:
    6256640
  • 财政年份:
    1991
  • 资助金额:
    $ 37.05万
  • 项目类别:
ACQUIRED IMMUNODEFICIENCY SYNDROME RESEARCH REVIEW
获得性免疫缺陷综合症研究综述
  • 批准号:
    2063342
  • 财政年份:
    1991
  • 资助金额:
    $ 37.05万
  • 项目类别:
ACQUIRED IMMUNODEFICIENCY SYNDROME REVIEW
获得性免疫缺陷综合症审查
  • 批准号:
    6091256
  • 财政年份:
    1991
  • 资助金额:
    $ 37.05万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了