Institut Pasteur, Université de Paris, CNRS UMR3569, Virus and Immunity Unit, 75015, Paris, France.
Université de Paris, École doctorale BioSPC 562, 75013, Paris, France.
Nat Commun. 2022 Feb 2;13(1):630. doi: 10.1038/s41467-022-28307-7.
Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. Beyond neutralization, bNAbs exert Fc-dependent functions including antibody-dependent cellular cytotoxicity and activation of the complement. Here, we show that a subset of bNAbs targeting the CD4 binding site and the V1/V2 or V3 loops inhibit viral release from infected cells. We combined immunofluorescence, scanning electron microscopy, transmission electron microscopy and immunogold staining to reveal that some bNAbs form large aggregates of virions at the surface of infected cells. This activity correlates with the capacity of bNAbs to bind to Env at the cell surface and to neutralize cell-free viral particles. We further show that antibody bivalency is required for viral retention, and that aggregated virions are neutralized. We have thus identified an additional antiviral activity of bNAbs, which block HIV-1 release by tethering viral particles at the surface of infected cells.
广谱中和抗体（bnAbs）针对 HIV-1 包膜糖蛋白（Env）是治疗或预防干预的有前途的分子。除中和作用外，bnAbs 还发挥 Fc 依赖性功能，包括抗体依赖性细胞毒性和补体激活。在这里，我们表明，一组针对 CD4 结合位点以及 V1/V2 或 V3 环的 bnAbs 抑制感染细胞中病毒的释放。我们结合免疫荧光、扫描电子显微镜、透射电子显微镜和免疫金染色，揭示了一些 bnAbs 在感染细胞表面形成大量病毒粒子的聚集物。这种活性与 bnAbs 在细胞表面结合 Env 和中和无细胞病毒颗粒的能力相关。我们进一步表明，抗体二价性是病毒保留所必需的，并且聚集的病毒粒子被中和。因此，我们已经确定了 bnAbs 的另一种抗病毒活性，通过将病毒粒子固定在感染细胞的表面来阻止 HIV-1 的释放。
