Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env
Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env
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DOI：
10.1128/jvi.00293-19
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发表时间：
2019-06-01
影响因子：
5.4
通讯作者：
Finzi, Andrs
中科院分区：
文献类型：
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作者：
Anand, Sai Priya;Grover, Jonathan R.;Finzi, Andrs
为了最大限度地减少对感染细胞的免疫反应，HIV-1限制了其包膜糖蛋白(Env)的表面表达。在这里，我们证明了这种机制是针对Env构象的，并影响抗体依赖的细胞毒性(ADCC)的效率。利用流式细胞术和共聚焦显微镜，我们发现针对封闭构象的Env的广谱中和抗体(BNAbs)可以诱导其从表面内化。相反，非中和抗体(NNAbs)在细胞表面显示的时间较长。阻断动力蛋白功能可以降低bNAb诱导的Env内化，从而使感染细胞对ADCC的易感性增加。我们的结果表明，抗体介导的Env内化是HIV-1用来逃避针对HIV-1感染细胞上表达的Env封闭构象的免疫反应的一种机制。在这项研究中，我们证明了抗体诱导的Env内化是构象特异性的，并降低了感染细胞对抗体依赖的细胞毒性(ADCC)的敏感性。Cc)因此，更好地了解这一机制可能有助于开发具有更强的介导ADCC能力的抗体。
To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here, we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of antibody-dependent cellular cytotoxicity (ADCC). Using flow cytometry and confocal microscopy, we show that broadly neutralizing antibodies (bNAbs) targeting the "closed" conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times. The bNAb-induced Env internalization can be decreased by blocking dynamin function, which translates into higher susceptibilities of infected cells to ADCC. Our results suggest that antibody-mediated Env internalization is a mechanism used by HIV-1 to evade immune responses against the "closed" conformation of Env expressed on HIV-1-infected cells.IMPORTANCE HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). cc) Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.