Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1
Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1
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DOI：
10.1128/jvi.80.5.2515-2528.2006
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发表时间：
2006-03-01
影响因子：
5.4
通讯作者：
Binley, JM
中科院分区：
文献类型：
--
作者：
Moore, PL;Crooks, ET;Binley, JM
人类免疫缺陷病毒I型(HIV-1)中和抗体被认为与非中和抗体的区别在于它们识别功能性gp120/gp41包膜糖蛋白(Env)三聚体的能力。到目前为止，由自然感染HIV-1或测试的候选疫苗诱导的抗体反应主要由非中和抗体组成。人们可能预计会有更有力的中和反应，特别是对带有功能三聚体的病毒颗粒。最近令人惊讶的观察到，非中和抗体可以特异性地捕获HIV-1，这可能提供了与这一悖论有关的线索。具体地说，有人认为非中和抗体可以与之结合的环境病毒形式存在于病毒表面。在这里，我们提出了HIV-1颗粒携带不起作用的gp120/gp41单体和gp120缺失的gp41残基的证据。使用天然的电泳带移位分析，我们表明抗体三聚体结合预测中和，并且非功能形式的Env可能解释非中和抗体捕获病毒的原因。我们推测，颗粒表面的这些非功能形式的Env有助于转移抗体反应，帮助病毒逃避中和。
Human immunodeficiency virus type I (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced by natural HIV-1 infection or by vaccine candidates tested to date consist largely of nonneutralizing antibodies. One might have expected a more vigorous neutralizing response, particularly against virus particles that bear functional trimers. The recent surprising observation that nonneutralizing antibodies can specifically capture HIV-1 may provide a clue relating to this paradox. Specifically, it was suggested that forms of Env, to which nonneutralizing antibodies can bind, exist on virus surfaces. Here, we present evidence that HIV-1 particles bear nonfunctional gp120/gp41 monomers and gp120-depleted gp41 stumps. Using a native electrophoresis band shift assay, we show that antibody-trimer binding predicts neutralization and that the nonfunctional forms of Env may account for virus capture by nonneutralizing antibodies. We hypothesize that these nonfunctional forms of Env on particle surfaces serve to divert the antibody response, helping the virus to evade neutralization.