Epitope target structures of Fc-mediated effector function during HIV-1 acquisition.
Epitope target structures of Fc-mediated effector function during HIV-1 acquisition.
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DOI：
10.1097/coh.0000000000000055
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发表时间：
2014-05
影响因子：
4.1
通讯作者：
Devico AL
中科院分区：
文献类型：
--
作者：
Lewis GK;Guan Y;Kamin-Lewis R;Sajadi M;Pazgier M;Devico AL
本文分析了最近的研究表明，HIV-1 Env三聚体中高度保守的表位是潜在的保护性非中和抗体介导的抗体依赖性细胞毒性（ADCC）的目标。最近在非人灵长类动物和人类中的研究表明，非中和抗体通过Fc介导的效应子功能，特别是ADCC，在阻断SHIV/SIV或HIV-1感染中发挥作用。此外，几项研究表明gp 120的C1区中的高度保守表位是这些抗体的靶点。然而，这些建议是有争议的，因为被动免疫研究并没有表明这种抗体可以阻止非人灵长类动物的获得。这种差异的潜在原因进行了讨论的结构背景下，有效的ADCC表位的靶细胞在狭窄的机会窗口，当抗体可以阻止HIV-1收购。累积的证据表明，除了病毒中和，Fc介导的效应器响应的高度保守的表位在HIV-1三聚体中发挥独特的作用，以及在阻断HIV-1收购重叠。证据将被讨论是否非中和抗体的HIV-1 Env三聚体，成为在病毒进入过程中暴露的表位显着有助于阻止HIV-1收购。
This review analyzes recent studies suggesting that highly conserved epitopes in the HIV-1 Env trimer are targets of potentially protective non-neutralizing antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC). Recent studies in both non-human primates and humans, suggest that non-neutralizing antibodies play a role in blocking infection with SHIV/SIV or HIV-1 by Fc-mediated effector function, in particular ADCC. Further, several studies implicate highly conserved epitopes in the C1 region of gp120 as targets of these antibodies. However, these suggestions are controversial, as passive immunization studies do not indicate that such antibodies can block acquisition in non-human primates. Potential reasons for this discrepancy are discussed in the structural context of potent ADCC epitopes on target cells during the narrow window of opportunity when antibodies can block HIV-1 acquisition. Cumulative evidence suggests that in addition to virus neutralization, Fc-mediated effector responses to highly conserved epitopes in the HIV-1 trimer play distinct as well as overlapping roles in blocking HIV-1 acquisition. Evidence will be discussed whether non-neutralizing antibodies specific for epitopes on the HIV-1 Env trimer that become exposed during viral entry contribute significantly to blocking HIV-1 acquisition.