Multiscale analysis of HIV-1-induced small T cell syncytia

HIV-1诱导的小T细胞合胞体的多尺度分析

基本信息

批准号：
10654070
负责人：
Markus Thali
金额：
$ 59.64万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10654070
关键词：
3-Dimensional AIDS/HIV problem Behavior Biochemical Biological Assay Cell Nucleus Cells Computer Analysis Data Evaluation Exploratory/Developmental Grant for Diagnostic Cancer Imaging Fostering Funding Giant Cells Grant HIV HIV-1 Heterogeneity Homeostasis Immune Immune response Impairment In Vitro Individual Infection Integration Host Factors Interruption Intervention Investigation Laboratories Lymphoid Tissue Maintenance Maps Minority Pathogenesis Phenotype Physiological Population Procedures Property Proteome Proteomics Public Health Publishing Resolution Role Secure Surface T-Lymphocyte Testing Therapeutic Universities Viral Virus Work antiretroviral therapy base cell motility cellular imaging design differential expression humanized mouse imaging study in vivo inflammatory milieu intravital imaging live cell imaging migration novel particle preservation prevent quantitative imaging recruit tool viral transmission

3-Dimensional AIDS/HIV problem Behavior Biochemical Biological Assay Cell Nucleus Cells Computer Analysis Data Evaluation Exploratory/Developmental Grant for Diagnostic Cancer Imaging Fostering Funding Giant Cells Grant HIV HIV-1 Heterogeneity Homeostasis Immune Immune response Impairment In Vitro Individual Infection Integration Host Factors Interruption Intervention Investigation Laboratories Lymphoid Tissue Maintenance Maps Minority Pathogenesis Phenotype Physiological Population Procedures Property Proteome Proteomics Public Health Publishing Resolution Role Secure Surface T-Lymphocyte Testing Therapeutic Universities Viral Virus Work antiretroviral therapy base cell motility cellular imaging design differential expression humanized mouse imaging study in vivo inflammatory milieu intravital imaging live cell imaging migration novel particle preservation prevent quantitative imaging recruit tool viral transmission

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项目摘要

HIV-1 dissemination critically depends on migration of infected T cells. Unexpectedly, a fraction of the infected T cells was recently found to exist as small syncytia, containing up to four nuclei. Importantly, these entities differ from larger syncytia which sometimes can be observed in late stages of virus dissemination/pathogenesis. Indeed, and as shown in three independent intravital imaging studies, they are present already at the earliest stages of infection. Our analyses in physiologically relevant in vitro settings further documented that small T cell syncytia can transfer virus to uninfected cells, suggesting that they can contribute to early virus dissemination. With this R01 application, we propose to start exploring whether HIV-1-induced small syncytia can indeed directly contribute to virus spread. We will start our investigations by characterizing motility/migration properties of syncytia and analyzing their role in virus transmission dynamics. Host and viral factors involved in homeostatic maintenance of the syncytial compartment will also be studied. Importantly, we have recruited the support of a leading HIV proteomics lab in order to comprehensively map the expression profiles of syncytia. Should the data resulting from this work support the hypothesis that syncytia contribute significantly to virus dissemination, we will pursue further funding in order to study potential strategies against these entities.

HIV-1传播严重取决于感染T细胞的迁移。出乎意料的是，一小部分最近发现被感染的T细胞作为小合胞体存在，最多包含四个核。重要的是，这些实体与较大的合成症不同，有时可以在病毒的后期观察到传播/发病机理。确实，如三个独立的浸润成像研究所示，它们已经存在于最早的感染阶段。我们在体外与生理相关的分析设置进一步记录了小型T细胞合成症可以将病毒转移到未感染的细胞中，这表明他们可以为早期的病毒传播做出贡献。使用此R01应用程序，我们建议开始探索HIV-1诱导的小型合成体是否可以确实，直接有助于病毒扩散。我们将通过表征来开始调查合成性的运动/迁移特性并分析其在病毒传播动力学中的作用。主持人还将研究参与稳态维护的病毒因素。重要的是，我们已经招募了领先的HIV蛋白质组学实验室的支持，以便全面绘制合成曲霉的表达曲线。这项工作产生的数据是否支持合成性的假设显着贡献病毒传播，我们将寻求进一步的资金，以研究针对这些的潜在策略实体。