Hughes Gareth J, Willey Samantha J, Cochrane Alexandra, Leen Clifford, Bell Jeanne E, Simmonds Peter
Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, UK.
AIDS. 2007 Jul 31;21(12):1507-13. doi: 10.1097/QAD.0b013e3281e209e6.
To demonstrate that HIV-1 immunocapture with an antibody against CD8 specifically captures virions derived from infected CD8 T cells, and to determine the proportion of HIV-1 derived from CD8 lymphocytes in plasma samples from HIV-infected individuals.
A virus capture method was developed to enable the detection of HIV-1 virions based upon the presence of certain cell-specific host-derived proteins (CD8, CD3, CD36) within the viral envelope. HIV-1 virions were captured using antibodies against these proteins and levels of bound virus were determined by quantitative reverse transcriptase-polymerase chain reaction. Highly pure CD8 and CD3+CD8- T-cell cultures were used as in-vitro models to determine the specificity of the virus capture technique.
The in-vitro model demonstrates that incorporation of the CD8 molecule into released virions is specific to infection of CD8 T cells. Levels of HIV-1 immunocaptured from plasma of infected individuals using the anti-CD8 antibody indicate that up to 15% (range 10-33) of the plasma viral load is derived from CD8 lymphocytes.
This study demonstrates for the first time that HIV-1-infected CD8 T cells can contribute substantially to levels of circulating virus during the course of infection. Levels of CD8-derived virus did not correlate with the level of infection of circulating CD8 T cells, but do show a significantly good fit to plasma viral loads based on a power model. The extensive infection of CD8 T cells implied by these results may contribute towards immune dysfunction and disease progression to AIDS.
证明使用抗CD8抗体进行HIV-1免疫捕获可特异性捕获源自受感染CD8 T细胞的病毒粒子，并确定HIV感染个体血浆样本中源自CD8淋巴细胞的HIV-1比例。
开发了一种病毒捕获方法，以基于病毒包膜内某些细胞特异性宿主衍生蛋白（CD8、CD3、CD36）的存在来检测HIV-1病毒粒子。使用针对这些蛋白的抗体捕获HIV-1病毒粒子，并通过定量逆转录酶-聚合酶链反应确定结合病毒的水平。使用高度纯化的CD8和CD3 + CD8-T细胞培养物作为体外模型来确定病毒捕获技术的特异性。
体外模型表明，CD8分子掺入释放的病毒粒子中是CD8 T细胞感染所特有的。使用抗CD8抗体从感染个体血浆中免疫捕获的HIV-1水平表明，血浆病毒载量中高达15%（范围10 - 33）源自CD8淋巴细胞。
本研究首次证明，在感染过程中，HIV-1感染的CD8 T细胞可对循环病毒水平有显著贡献。源自CD8的病毒水平与循环CD8 T细胞的感染水平无关，但基于幂模型确实与血浆病毒载量显示出显著的良好拟合。这些结果所暗示的CD8 T细胞的广泛感染可能导致免疫功能障碍和疾病进展至艾滋病。
