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

• 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
• 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

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的传播严重依赖于受感染T细胞的迁移。没想到，只有一小部分