HIV-1 ENVELOPE. Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein.
HIV-1 ENVELOPE. Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein.
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DOI：
10.1126/science.aaa9804
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发表时间：
2015-07-10
期刊：
影响因子：
--
通讯作者：
Chen B
中科院分区：
文献类型：
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作者：
Chen J;Kovacs JM;Peng H;Rits-Volloch S;Lu J;Park D;Zablowsky E;Seaman MS;Chen B
HIV-1疫苗开发的一个主要目标是产生一种免疫原，以模拟病毒体表面上的天然、功能性HIV-1包膜三聚体刺突（Env）。然而，由于大多数制剂固有的不稳定性和异质性，我们缺乏对天然功能性三聚体的可靠描述。我们在这里描述了两个构象均匀的Envs来自难以中和的主要分离株。它们的所有非中和表位都是完全隐藏的，并且不依赖于它们的蛋白水解加工。大多数广泛中和抗体（bnAb）识别这些天然三聚体。其胞质尾区的截短对膜融合几乎没有影响，但它减少了与三聚体特异性bnAb的结合，同时暴露了非中和表位。这些结果产生了比迄今为止真正未触发和功能性HIV-1 Env更准确的抗原图;它们可以指导有效的疫苗开发。
A major goal for HIV-1 vaccine development is the production of an immunogen to mimic native, functional HIV-1 envelope trimeric spikes (Env) on the virion surface. We lack a reliable description of a native, functional trimer, however, because of inherent instability and heterogeneity in most preparations. We describe here two conformationally homogeneous Envs derived from difficult-to-neutralize primary isolates. All their non-neutralizing epitopes are fully concealed and independent of their proteolytic processing. Most broadly neutralizing antibodies (bnAbs) recognize these native trimers. Truncation of their cytoplasmic tail has little effect on membrane fusion, but it diminishes binding to trimer-specific bnAbs while exposing non-neutralizing epitopes. These results yield a more accurate antigenic picture than hitherto possible of a genuinely untriggered and functional HIV-1 Env; they can guide effective vaccine development.