Anzinger Joshua J, Olinger Gene G, Spear Gregory T
Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 5N111, Bethesda, Maryland 20892, USA.
Virol J. 2008 Aug 15;5:95. doi: 10.1186/1743-422X-5-95.
HIV infection of cells varies greatly between individuals, with multiple steps in the replication cycle potentially contributing to the variability. Although entry and post-entry variability of HIV infection levels in cells has been demonstrated, variability in HIV binding has not been examined. In this study, we examined variability of HIV binding to peripheral blood mononuclear cells (PBMC) from different donors.
HIV binding to PBMC varied up to 3.9-fold between individuals and was independent of CD4. Replication of HIV in donor PBMC required CD4 and paralleled virus binding trends of donor PBMC. To assess the stability of virus binding phenotypes over time, HIV was bound to donors with low- and high-binding phenotypes. The binding phenotypes were maintained when tested weekly over a 4-week period for 3 of 4 donors, while one high-binding donor decreased to lower binding on the 4th week. The low- and high-binding phenotypes were also preserved across different HIV strains. Experiments performed to determine if there was an association between HIV binding levels and specific cell subset levels within PBMC showed no correlation, suggesting that HIV binds to multiple cell subsets.
These results show that differences exist in HIV binding to donor PBMC. Our data also show that HIV binding to donor PBMC is CD4-independent and can change over time, suggesting that virus binding variability is due to differences in the expression of changeable cell-surface host factors. Taken together, this study highlights the impact of cell-surface factors in HIV binding to, and infection of, PBMC which likely represents an important step in HIV infection in vivo.
细胞的HIV感染在个体间差异很大,复制周期中的多个步骤可能导致这种变异性。尽管已经证明了细胞中HIV感染水平在进入和进入后存在变异性,但尚未研究HIV结合的变异性。在本研究中,我们检测了HIV与来自不同供体的外周血单核细胞(PBMC)结合的变异性。
HIV与PBMC的结合在个体间差异高达3.9倍,且与CD4无关。HIV在供体PBMC中的复制需要CD4,并与供体PBMC的病毒结合趋势平行。为了评估病毒结合表型随时间的稳定性,将HIV与具有低结合和高结合表型的供体结合。在4周内每周进行检测时,4名供体中有3名的结合表型得以维持,而一名高结合供体在第4周时结合能力下降。低结合和高结合表型在不同HIV毒株中也得以保留。为确定HIV结合水平与PBMC内特定细胞亚群水平之间是否存在关联而进行的实验未显示出相关性,这表明HIV可与多个细胞亚群结合。
这些结果表明,HIV与供体PBMC的结合存在差异。我们的数据还表明,HIV与供体PBMC的结合不依赖于CD4,并且会随时间变化,这表明病毒结合变异性是由于可变细胞表面宿主因子表达的差异所致。综上所述,本研究突出了细胞表面因子在HIV与PBMC结合及感染中的作用,这可能是HIV体内感染的一个重要步骤。