Donor variability in HIV binding to peripheral blood mononuclear cells

Donor variability in HIV binding to peripheral blood mononuclear cells
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DOI:
10.1186/1743-422x-5-95
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发表时间:
2008-08-15
期刊:
影响因子:
4.8
通讯作者:
Spear, Gregory T.
Spear, Gregory T.
中科院分区:
医学3区
文献类型:
--
作者:
Anzinger, Joshua J.;Olinger, Gene G.;Spear, Gregory T.

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背景资料:HIV感染细胞在个体之间差异很大,复制周期中的多个步骤可能导致变异性。虽然已经证明了细胞中HIV感染水平的进入和进入后的变异性,但尚未检查HIV结合的变异性。在这项研究中,我们研究了艾滋病毒结合外周血单核细胞(PBMC)从不同的donators.Results的变异性:艾滋病毒结合PBMC变化高达3.9倍之间的个人和独立的CD4。HIV在供体PBMC中的复制需要供体PBMC的CD4和HIV病毒结合趋势。为了评估病毒结合表型随时间的稳定性,将HIV与具有低结合表型和高结合表型的供体结合。当在4周期间每周测试4个供体中的3个时,保持结合表型,而一个高结合供体在第4周降低至较低结合。低结合和高结合表型也在不同的HIV毒株中保留。进行实验,以确定是否有一个关联HIV结合水平和特定的细胞亚群水平在PBMC内显示没有相关性,这表明,HIV结合到多个细胞subsets.Conclusion:这些结果表明,存在差异,在HIV结合到供体PBMC。我们的数据还表明,HIV与供体PBMC的结合是不依赖于CD4的,并且可以随着时间的推移而改变,这表明病毒结合的可变性是由于可变的细胞表面宿主因子表达的差异。总之,这项研究突出了细胞表面因子在HIV结合和感染PBMC中的影响,这可能代表了体内HIV感染的重要步骤。
Background: 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.Results: 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.Conclusion: 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 cellsurface 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.