课题基金 / 基金详情

Multiscale analysis of HIV-1 assembly, release, and cell-to-cell transmission

Multiscale analysis of HIV-1 assembly, release, and cell-to-cell transmission
HIV-1 组装、释放和细胞间传播的多尺度分析
批准号:
9295126
负责人:
Markus Thali
金额:
$8.13万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-04-22 至 2019-08-31

项目摘要

项目成果

Markus Thali的其他基金

相似基金

相关文献

中文摘要
翻译
HIV-1在感染者中迅速传播。这至少可以部分归因于病毒的传播。 在T淋巴细胞之间,当感染和未感染的T细胞直接接触时,这种情况发生得非常有效 从而形成所谓的病毒学突触(VS)。虽然这种瞬时粘连的许多特征 结构仍未确定,我们知道VS的形成需要病毒包膜的相互作用 糖蛋白(Env),在受感染的(产生病毒的)细胞表面表达,与病毒受体 在未感染的(目标)细胞上。然而,目前还不清楚为什么环境和环境之间的相互作用 病毒颗粒与靶细胞膜的融合,以及病毒受体/辅助受体通常不会产生 在生产者-靶细胞融合中,从而形成合胞体。以小T细胞为基础的合胞体 在感染者的淋巴结和人源化的小鼠中观察到,但显然大多数人遇到的 感染和未感染的细胞之间没有融合。事实上,它们之间没有聚变的遭遇 细胞是HIV-1致病机制三个中心特征的必要条件:细胞到细胞的传播,杀伤 旁观者细胞,以及建立和维持潜伏感染的T淋巴细胞库。因此, 揭示感染和未感染细胞之间的融合是如何受到调控的不仅有助于我们的 关于病毒如何在细胞间有效传播的知识,也将有助于理解 HIV-1致病机制的关键方面。因此,我们建议研究细胞内在的和细胞外的 这些因素共同促进了病毒转移时产生细胞和目标细胞的分离。它还将接受测试 如果细胞之间的融合超过正常水平,是否不利于病毒的传播。
英文摘要
HIV-1 disseminates rapidly in infected individuals. This can at least partially be attributed to virus transfer between T lymphocytes, which occurs very efficiently when infected and uninfected T cells directly contact each other, thus forming the so-called virological synapse (VS). While many features of this transient adhesion structure remain undefined, we know that VS formation necessitates an interaction of the viral envelope glycoprotein (Env), which is expressed at the surface of infected (virus producing) cells, with the viral receptor on uninfected (target) cells. It is not understood, however, why such interactions between Env, which mediates fusion of the viral particle with target cell membranes, and the viral receptor/coreceptor do not routinely result in producer-target cell fusion and thus the formation of a syncytium. Small T cell-based syncytia have been observed in lymph nodes of infected individuals and in humanized mice, but it is evident that most encounters between infected and uninfected cells resolve without fusion. Indeed, fusion-less encounters between these cells are a sine qua non for three central features of HIV-1 pathogenesis: cell-to-cell transmission, killing of bystander cells, and establishment and maintenance of a reservoir of latently infected T lymphocytes. Hence, revealing how fusion between infected and uninfected cells is regulated will not only contribute to our knowledge about how the virus can be efficiently transmitted from cell to cell, it will also aid understanding of key aspects of HIV-1 pathogenesis. We thus propose to investigate how both cell-intrinsic and cell-extrinsic factors, together, facilitate disengagement of producer and target cells upon virus transfer. It will also be tested whether enhancing fusion between the cells beyond the normal level is detrimental to virus dissemination.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Multiscale analysis of HIV-1-induced small T cell syncytia
Multiscale analysis of HIV-1-induced small T cell syncytia
The Host Response Against HIV-1-induced T Cell Syncytia
The Host Response Against HIV-1-induced T Cell Syncytia
海外基金