Elimination of HIV-1-infected cells by broadly neutralizing antibodies.
Elimination of HIV-1-infected cells by broadly neutralizing antibodies.
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DOI：
10.1038/ncomms10844
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发表时间：
2016-03-03
影响因子：
16.6
通讯作者：
Schwartz O
中科院分区：
文献类型：
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作者：
Bruel T;Guivel-Benhassine F;Amraoui S;Malbec M;Richard L;Bourdic K;Donahue DA;Lorin V;Casartelli N;Noël N;Lambotte O;Mouquet H;Schwartz O
HIV-1 env特异性广泛中和抗体（bNAbs）的Fc区是抑制病毒血症所必需的，其机制尚不清楚。在这里，我们发现了在细胞培养中发挥抗体依赖性细胞毒性（ADCC）并通过自然杀伤（NK）作用杀死hiv -1感染淋巴细胞的bNAbs。这些抗体靶向cd4结合位点，gp120上的聚糖/V3和V1/V2环，或gp41片段。Env表位暴露在表面的景观和感染细胞对ADCC的敏感性在不同的病毒株之间差异很大。有效的ADCC需要bNAbs与Env持续的细胞表面结合，并且结合bNAbs具有强大的杀伤活性。此外，来自hiv阳性个体的被重新激活的感染细胞暴露出异质的Env表位模式，其水平通常但并不总是足以触发bNAbs的杀伤。我们的研究描述了控制bNAbs ADCC活性的参数，并支持使用最有效的抗体来清除病毒库。广泛中和抗体（bNAbs）有望成为针对HIV-1的潜在治疗方法，但其整体抗病毒活性仍有待充分阐明。在这里，作者评估了一组bNAbs触发抗体依赖性细胞毒性的能力，并确定了最有效的抗体组合。
The Fc region of HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) is required for suppressing viraemia, through mechanisms which remain poorly understood. Here, we identify bNAbs that exert antibody-dependent cellular cytotoxicity (ADCC) in cell culture and kill HIV-1-infected lymphocytes through natural killer (NK) engagement. These antibodies target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The landscape of Env epitope exposure at the surface and the sensitivity of infected cells to ADCC vary considerably between viral strains. Efficient ADCC requires sustained cell surface binding of bNAbs to Env, and combining bNAbs allows a potent killing activity. Furthermore, reactivated infected cells from HIV-positive individuals expose heterogeneous Env epitope patterns, with levels that are often but not always sufficient to trigger killing by bNAbs. Our study delineates the parameters controlling ADCC activity of bNAbs, and supports the use of the most potent antibodies to clear the viral reservoir. Broadly neutralizing antibodies (bNAbs) are promising as potential therapies targeting HIV-1 but their overall antiviral activity remains to be fully elucidated. Here the authors evaluate the ability of a panel of bNAbs to trigger antibody-dependent cellular cytotoxicity and identify the most effective antibody combinations.