A cell-to-cell HIV transfer assay identifies humoral responses with broad neutralization activity
A cell-to-cell HIV transfer assay identifies humoral responses with broad neutralization activity
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DOI：
10.1016/j.vaccine.2011.05.016
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发表时间：
2011-07-18
期刊：
影响因子：
5.5
通讯作者：
Blanco, Julia
中科院分区：
文献类型：
--
作者：
Sanchez-Palomino, Sonsoles;Massanella, Marta;Blanco, Julia
背景资料：细胞到细胞的HIV传播通过病毒学突触进行两个步骤，首先HIV颗粒迅速转移到靶细胞中的CD 4依赖的方式，然后辅受体依赖的事件允许单个靶细胞的感染或死亡和细胞到细胞fusion.Methods：293 T或MOLT细胞产生的HIV颗粒与原代CD 4 T细胞或报告细胞系共培养。评估了HIV转移、细胞融合和靶细胞死亡的程度。从19个HIV感染者的血清的抑制进行了评估，并与无细胞的HIV中和使用不同的信封从A，B，C和E.结果：血清显示出不同的能力，以保护CD 4 T细胞从细胞到细胞的转移，融合或死亡时，与HIV生产的293 T细胞共培养。一些血清能够阻断所有参数（IgGb 12的特性），而另一些血清尽管能够阻断融合和死亡（抗体阻断后CD 4结合步骤的特性），但显示出较低的抗HIV转移活性。细胞间HIV转移的中和与IgG结合天然Env强烈相关。有趣的是，有效阻断HIV转移的血清显示出更广泛的中和反应，因为与显示低CD 4结合位点反应的血清相比，它们中和了更高百分比的测试病毒（P = 0.01）。在T细胞-T细胞HIV传播的模型中观察到类似的结果，尽管该实验模型显示出较低的能力来区分广泛中和respons.Conclusion：细胞-细胞HIV转移测定确定具有广泛中和能力的血清，并可能有助于表征抗HIV体液反应。(C)2011爱思唯尔有限公司保留所有权利。
Background: Cell-to-cell HIV spread through virological synapses proceeds in two steps, first HIV particles are rapidly transferred to target cells in a CD4-dependent manner and then coreceptor-dependent events allow for infection or death of single target cells and cell-to-cell fusion.Methods: 293T or MOLT cells producing HIV particles were cocultured with primary CD4 T-cells or reporter cell lines. The extent of HIV transfer, cell fusion and target cell death was assessed. Inhibition by sera from 19 HIV-infected patients was evaluated and compared with cell-free HIV neutralization using different envelopes from clades A, B, C and E.Results: Sera showed different abilities to protect CD4 T-cells from cell-to-cell transfer, fusion or death when cocultured with HIV producing 293T cells. Some sera were able to block all parameters (a property of IgGb12), while other showed lower activity against HIV transfer despite being able to block fusion and death (a property of antibodies blocking post-CD4 binding steps). Neutralization of cell-to-cell HIV transfer strongly correlated with IgG binding to native Env. Interestingly, sera that efficiently blocked HIV transfer showed broader neutralizing response, as they neutralized a higher percentage of the viruses tested compared with sera showing low CD4 binding site responses (P = 0.01). Similar results were observed in a model of T cell-T cell HIV transmission, although this experimental model showed lower capacity to discriminate broadly neutralizing responses.Conclusion: Cell-to-cell HIV transfer assays identify sera with broadly neutralizing capacity and may help to characterize anti-HIV humoral responses. (C) 2011 Elsevier Ltd. All rights reserved.