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Regulation of Cofilin in HIV-1 Infection of Human CD4 T Cells

Cofilin 在人类 CD4 T 细胞 HIV-1 感染中的调节

基本信息

批准号：
8277404
负责人：
YUNTAO WU
金额：
$ 30.52万
依托单位：
GEORGE MASON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-03 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8277404
关键词：
Acquired Immunodeficiency Syndrome Actins Address Alanine Amino Acids Binding Biological Testing CD4 Positive T Lymphocytes CXCR4 Receptors CXCR4 gene Cells Chemotaxis Complex Data Event F-Actin G Protein-Coupled Receptor Signaling Glycoproteins Goals HIV HIV Envelope Protein gp120 HIV Infections HIV-1 Human Immigration Immunologic Deficiency Syndromes Infection Knowledge LIM Domain Kinase 1 Laboratories Laboratory Research Lead Maps Measures Mediating Methods Modeling Molecular Molecular Medicine Monitor Mutagenesis Mutate Nuclear Pathway interactions Pertussis Toxin Phosphoproteins Phosphoric Monoester Hydrolases Phosphorylation Play Positioning Attribute Postdoctoral Fellow Principal Investigator Process Protein Dephosphorylation Protein Family Protein Phosphatase 2A Regulatory Subunit PR53 Proteomics Regulation Research Research Personnel Rest Reverse Transcription Role Scanning Serine Signal Pathway Signal Transduction Signaling Molecule Small Interfering RNA Stream T-Cell Activation T-Cell Depletion T-Lymphocyte Testing Threonine Time United States National Institutes of Health Universities V3 Loop Viral Viral Pathogenesis Virus Virus Diseases Work actin depolymerizing factor base chemokine chemokine receptor cofilin env Genes experience gel electrophoresis knock-down latent infection member migration new therapeutic target phosphatase inhibitor rho tool

项目摘要

Project Summary: HIV-1 infects CD4 T cells and causes T cell depletion and immunodeficiency. Molecular interactions between the virus and T cells that occur at the early time are critical for viral infection and pathogenesis. Our preliminary studies have identified cofilin as one of the early signaling molecules targeted by the virus in order to establish latent infection of CD4 T cells. We have demonstrated that HIV-1 utilizes the viral envelope/CXCR4 signaling to activate cofilin in order to overcome the cortical actin restriction in resting CD4 T cells. This molecular event is necessary for viral nuclear migration in resting T cells. Our long-term goal is to study the molecular details of viral-host interaction that lead to aberrant signaling and cofilin activation. The specific aims of this proposal are to study the interactions between the viral envelope, gp120, and its chemokine coreceptor, CXCR4, that lead to cofilin activation. We will identify the signaling domains on gp120, as well as map the signaling pathways involved. This proposed research is significant because the information will help to identify specific cellular mechanisms hijacked by the virus to facilitate infection. These mechanisms are highly relevant to viral pathogenesis in CD4 T cells. Results from the proposed study may also identify novel therapeutic targets to inhibit viral infection.

项目概要： HIV-1感染CD 4 T细胞并导致T细胞耗竭和免疫缺陷。分子病毒和T细胞之间的相互作用发生在早期，感染和发病机制。我们的初步研究已经确定cofilin是病毒靶向的早期信号分子，以建立潜伏感染， CD 4 T细胞。我们已经证明，HIV-1利用病毒包膜/CXCR 4 信号传导以激活cofilin以克服静息时皮质肌动蛋白的限制 CD 4 T细胞。这一分子事件是必要的病毒核迁移在静息T 细胞我们的长期目标是研究病毒与宿主相互作用的分子细节，导致异常信号传导和cofilin激活。这项建议的具体目标是研究病毒包膜，gp 120，及其趋化因子辅助受体之间的相互作用， CXCR 4，导致cofilin激活。我们将识别gp 120上的信号结构域，以及绘制相关的信号通路。这项研究具有重要意义因为这些信息将有助于识别被病毒劫持的特定细胞机制，病毒，以促进感染。这些机制与病毒的发病机制高度相关 CD 4 T细胞。拟议研究的结果也可能发现新的治疗方法，以抑制病毒感染。