CCR5 and CXCR4 tropism and CD4 kinetics in HIV-1 infection

HIV感染通过逐渐消耗特定类型的免疫细胞的数量而引起疾病，CD 4细胞？我们还不完全了解感染如何导致CD 4细胞随时间推移而丢失。虽然艾滋病毒直接感染并破坏CD 4细胞，但身体通常只是制造更多的细胞来取代丢失的细胞。我们认为是什么决定了艾滋病毒如何影响身体？s CD 4细胞正是它感染的细胞类型。有几种类型的CD 4细胞。不同的病毒株根据细胞表面的受体（如锁定装置）偏好感染不同亚型的CD 4细胞。两个受体，？CCR5？然后呢？CXCR4？，显得尤为重要。我们假设病毒CCR 5/CXCR 4偏好（？向性？），感染细胞的类型和这些细胞分裂的速度决定了HIV对CD 4细胞数量的长期影响。为了研究这个概念，我们将测量不同亚型的CD 4细胞在体内分裂和消失的速度。虽然从试管中的细胞和病毒研究中已经学到了很多，但要回答关于CD 4损失的问题，只能通过研究艾滋病毒感染者体内的病毒和CD 4细胞来完成。我们最近开发了一种使用含有过量氘的葡萄糖来实现这一点的方法。氘是一种天然存在的氢的非放射性形式（或同位素），其行为与氢完全相似，但可以使用质谱仪测量。我们将把氘标记的葡萄糖（这是无害的）作为一种饮料（每半小时10小时）给艾滋病毒感染者，然后在接下来的3周内采集血液样本。葡萄糖被分裂细胞（而不是非分裂细胞）用来制造新的DNA。通过将细胞分成亚型并使用质谱仪测量其DNA中的氘，我们可以测量CD 4亚型分裂的速度以及它们在体内存活的时间。我们还将在血液中测试病毒的CCR 5/CXCR 4嗜性。我们将把结果与一组没有感染艾滋病毒的人的结果进行比较。我们将使用这些测量来创建一个数学图像或？模特？HIV如何与不同的免疫细胞相互作用，以解释为什么CD 4细胞随着时间的推移而缓慢被破坏，以及为什么病毒嗜性的变化会引发CD 4细胞的加速损失。

HIV infection causes disease by progressively depleting the number of a particular type of immune cells, ?CD4 cells?. We do not fully understand how infection results in loss of CD4 cells over time. Although HIV infects and destroys CD4 cells directly, the body normally just makes more cells to replace the lost ones. We believe that what determines how HIV affects the body?s CD4 cells is the exact type of cell it infects. There are several sub-types of CD4 cells. Different strains of virus prefer to infect different sub-types of CD4 cell according to the receptors (like locking devices) on the cell surface. Two receptors, ?CCR5? and ?CXCR4?, appear particularly important. We hypothesise that the interaction between the viral CCR5/CXCR4 preference (?tropism?), the type of cell infected and the speed at which those cells are dividing determines the long-term effect of HIV on CD4 cell numbers. To investigate this concept, we will measure how fast different sub-types of CD4 cells are dividing and disappearing within the body. Although much has been learnt from investigating cells and viruses in test tubes, answering such questions about CD4 loss can only be done by studying virus and CD4 cells within the body of people infected with HIV. We have recently developed a way of doing this using glucose containing an excess of deuterium. Deuterium is a naturally-occurring non-radioactive form (or isotope) of hydrogen which behaves exactly like hydrogen but can be measured using a mass spectrometer. We will give deuterium-labelled glucose (which is harmless) as a drink (half-hourly for 10 hours) to people with HIV infection, then take blood samples over the following 3 weeks. The glucose is used by dividing, but not non-dividing, cells to make new DNA. By separating the cells into their subtypes and measuring the deuterium in their DNA using a mass spectrometer, we can measure how fast CD4 subtypes divide and how long they survive in the body. We will also test the virus in the bloodstream for its CCR5/CXCR4 tropism. We will compare the results to those from a group of people without HIV infection. We will use these measurements to create a mathematical picture or ?model? of how HIV interacts with different immune cells to explain why CD4 cells are destroyed slowly over time and why changes in viral tropism trigger accelerated loss of CD4 cells.