Infection of CD8 lymphocytes by HIV-1 in the aetiology of AIDS
Infection of CD8 lymphocytes by HIV-1 in the aetiology of AIDS
批准号:
G0800176/1
负责人:
Peter Simmonds
金额:
$73.75万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2009
资助国家:
英国
项目状态:
已结题
起止时间:
2009 至 --
中文摘要
尽管经过几十年的研究,艾滋病毒究竟是如何导致艾滋病的还没有完全弄清楚。在艾滋病中,免疫系统被艾滋病毒严重破坏,使感染者容易受到一系列感染,有时可能是致命的癌症,如果不治疗。众所周知,CD4(或辅助性T细胞)淋巴细胞是感染者体内HIV的主要靶点。这是因为这种细胞类型在其细胞表面表达HIV附着并最终穿透和感染细胞所需的CD4蛋白。CD4淋巴细胞的感染和破坏对免疫系统是极其有害的,因为这种细胞类型在各种类型的免疫应答中起着关键作用,例如抗病毒细胞毒性T细胞活性和抗体产生(因此其名称为a?帮手?细胞)。最近,我们发现另一种类型的淋巴细胞,CD8淋巴细胞,也可能被艾滋病毒感染。这种细胞类型是免疫系统的关键部分?在实验室条件下,当对外来目标(如入侵的微生物或病毒)做出反应时,已经显示出对感染的敏感性。从目前收集到的数据来看,艾滋病毒对这种细胞类型的感染和破坏可能是艾滋病免疫系统崩溃的另一个重要原因。当艾滋病毒感染一个细胞时,病毒复制的过程产生大量新的感染性病毒,这些病毒从细胞表面发芽,感染更多的细胞。在这个萌芽过程中,HIV可能会获得一些细胞蛋白质,通常是偶然的,有时是故意的。因此,在病毒包膜中发现的细胞蛋白类型可以显示感染的细胞类型。例如,HIV通常含有一种称为CD36的细胞表面蛋白,这种蛋白质仅在巨噬细胞中发现。我们已经发现,CD8也可能经常被感染CD8淋巴细胞的病毒掺入。使用这些细胞蛋白作为标记,我们可以分析感染个体血浆中的病毒,以确定哪些细胞被感染。因此,我们可以确定CD4,CD8和巨噬细胞被HIV靶向的程度,以及在HIV感染的各个阶段,从急性感染到AIDS,哪种是最重要的感染细胞类型。使用这种新方法来研究病毒在感染个体中的复制将对研究艾滋病患者如何无法控制艾滋病毒和其他感染具有重要意义。
英文摘要
Despite many decades of research, how exactly HIV causes AIDS is not fully understood. In AIDS, the immune system is profoundly damaged by HIV, leaving the infected person susceptible to a range of infections and sometimes cancers that may be fatal if untreated. It is known that CD4 (or T-helper) lymphocytes are a major target for HIV in the infected person. This is because this cell type expresses on its cell surface the CD4 protein that HIV needs to attach and ultimately penetrate and infect the cell. Infection and destruction of CD4 lymphocytes is extremely damaging to the immune system, because this cell type plays a key role in various types of immune responses, such as antiviral cytotoxic T cell activity and antibody production (hence its name as a ?helper? cell). Recently, we have found that another type of lymphocyte, the CD8 lymphocyte, may also be infected by HIV. This cell type is a key part of the immune system?s response to infections, and in laboratory conditions, has been shown to become vulnerable to infection when reacting to a foreign target, such as an invading microbe or virus. From the data collected so far, infection and destruction of this cell type by HIV may be an important additional cause of the collapse of the immune system in AIDS.When HIV infects a cell, the process of virus replication generates large numbers of new infectious viruses that bud from the cell surface to infect further cells. During this budding process, HIV may acquire a number of cellular proteins, often accidentally, sometimes deliberately. The type of cellular proteins found in virus envelopes therefore can show what cell type was infected. For example, HIV frequently contains a cell surface protein called CD36, a protein that is only found in macrophages. We have found that CD8 may also be frequently incorporated by viruses infecting CD8 lymphocytes. Using these cellular proteins as markers, we can analyse virus in plasma of infected individuals to determine which cells were infected. We can therefore determine to extent to which CD4, CD8 and macrophages are targeted by HIV, and which is most important infected cell type at various stages of HIV infection, ranging from acute infection through to AIDS. The use of this new method to study virus replication in infected individuals will be of importance investigating how individuals with AIDS become unable to control HIV and other infections.
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批准号:MR/P011128/1
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项目类别:Research Grant
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资助金额:$85.26万
-
财政年份:2017
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负责人:Peter Simmonds
-
依托单位:
国内基金
海外基金
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