ROLE OF MEMORY T CELL DYNAMICS IN SIV INFECTION

记忆 T 细胞动力学在 SIV 感染中的作用

• 批准号: 7715890
• 负责人: Louis J. Picker
• 金额: $ 17.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715890
• 关键词: CCR5 gene; Cells; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Data; Deterioration; Disease Progression; Documentation; Funding; Generations; Goals; Grant; HIV Infections; Human; Infection; Institution; Integration Host Factors; Macaca mulatta; Memory; Nature; Opportunistic Infections; Outcome; Phase; Play; Population; Production; Regulation; Research; Research Personnel; Resources; Role; SIV; Source; Staging; T cell regulation; T-Lymphocyte; United States National Institutes of Health; Viral; Virus; immune function; memory CD4 T lymphocyte

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the absence of treatment, infection of rhesus macaques with pathogenic SIV, like HIV infection of humans, is almost always progressive with deterioration of immune function, and ultimately death due to either direct consequences of SIV itself or opportunistic infection. The tempo of progression, however, varies considerably from host to host, even with cloned virus, suggesting that host factors play a role in supporting and/or mitigating the extent and consequences of viral replication. Recent documentation of massive, systemic depletion of SIV "target" cells (CCR5+, CD4+ memory T cells) in early SIVmac239 infection, and a concomitant, profound increase in the production and turnover of this population suggests that target cell availability and mechanisms of target cell generation may significantly contribute to the outcome of infection. Indeed, our preliminary data suggest that plateau-phase viral replication may be largely supported by infection of "new" T cell targets generated by this marked increase CD4+ memory T cell turnover. The overall goal of this project is therefore to characterize the nature and regulation of T cell turnover in various stages of SIV infection, and to ascertain the impact of this regulation on viral dynamics and disease progression.

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在没有治疗的情况下，致病性SIV感染恒河猴，就像人类的HIV感染一样，几乎总是随着免疫功能的恶化而进行性的，最终由于SIV本身的直接后果或机会性感染而死亡。 然而，进展的克里思，从主机到主机，甚至与克隆的病毒，有很大的不同，这表明，主机的因素发挥作用，支持和/或减轻病毒复制的程度和后果。 最近的文献表明，在早期SIVmac 239感染中，SIV“靶”细胞（CCR 5+，CD 4+记忆T细胞）的大规模全身性耗竭，以及伴随的该群体的产生和周转的显著增加，表明靶细胞的可用性和靶细胞产生的机制可能显著有助于感染的结果。事实上，我们的初步数据表明，平台期病毒复制可能在很大程度上得到了由这种显著增加的CD 4+记忆T细胞周转产生的“新”T细胞靶标感染的支持。因此，该项目的总体目标是表征SIV感染的各个阶段中T细胞周转的性质和调节，并确定这种调节对病毒动力学和疾病进展的影响。