Veillette Maxime, Richard Jonathan, Pazgier Marzena, Lewis George K, Parsons Matthew S, Finzi Andrés
Centre de recherche du CHUM (CRCHUM), 900 St-Denis street, Tour Viger, R09.420, Montreal, Quebec, H2X 0A9, Canada.
Curr HIV Res. 2016;14(1):9-23. doi: 10.2174/1570162x13666150827093449.
The role of antibody Fc-mediated effector functions in controlling or preventing infections by human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) viruses has been recently highlighted in multiple studies. One of those effector functions, antibody-dependent cellular cytotoxicity (ADCC) was suggested as correlating with decreased HIV-1 acquisition risk in the recent Thai RV144 vaccine trial. RV144-elicited antibodies with potent ADCC activity were recently found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction. However, HIV-1 efficiently limits the exposure of those epitopes by strongly downregulating CD4 by both Nef and Vpu accessory proteins, as well as indirectly preventing the accumulation of Env at the cell surface by Vpu-mediated BST-2 antagonism. These accessory proteins were thus proposed to play a critical role in decreasing the susceptibility of HIV-infected cells to elimination by ADCC. In this review we will summarize these recent findings and discuss the critical role that HIV-1 envelope glycoproteins conformation plays on ADCC responses, how these responses can be measured in the laboratory, the role of HIV-1-transmission on ADCC responses and how this knowledge can be used to develop new strategies aimed at targeting HIV-1-infected cells.
抗体Fc介导的效应功能在控制或预防人类免疫缺陷病毒1型（HIV-1）和猿猴免疫缺陷病毒（SIV）感染中的作用，最近在多项研究中得到了突出体现。在最近的泰国RV144疫苗试验中，其中一种效应功能，即抗体依赖性细胞毒性（ADCC）被认为与降低HIV-1感染风险相关。最近发现，RV144诱导产生的具有强大ADCC活性的抗体能够识别Env-CD4相互作用后暴露的HIV包膜（Env）表位。然而，HIV-1通过Nef和Vpu辅助蛋白强烈下调CD4，以及通过Vpu介导的BST-2拮抗作用间接阻止Env在细胞表面的积累，从而有效地限制了这些表位的暴露。因此，这些辅助蛋白被认为在降低HIV感染细胞对ADCC清除的敏感性方面起着关键作用。在这篇综述中，我们将总结这些最新发现，并讨论HIV-1包膜糖蛋白构象在ADCC反应中所起的关键作用、如何在实验室中检测这些反应、HIV-1传播对ADCC反应的作用，以及如何利用这些知识来制定针对HIV-1感染细胞的新策略。
