Frey Gary, Peng Hanqin, Rits-Volloch Sophia, Morelli Marco, Cheng Yifan, Chen Bing
Laboratory of Molecular Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3739-44. doi: 10.1073/pnas.0800255105. Epub 2008 Mar 5.
Most antibodies induced by HIV-1 are ineffective at preventing initiation or spread of infection because they are either nonneutralizing or narrowly isolate-specific. Rare, "broadly neutralizing" antibodies have been detected that recognize relatively conserved regions on the envelope glycoprotein. Using stringently characterized, homogeneous preparations of trimeric HIV-1 envelope protein in relevant conformations, we have analyzed the molecular mechanism of neutralization by two of these antibodies, 2F5 and 4E10. We find that their epitopes, in the membrane-proximal segment of the envelope protein ectodomain, are exposed only on a form designed to mimic an intermediate state during viral entry. These results help explain the rarity of 2F5- and 4E10-like antibody responses and suggest a strategy for eliciting them.
大多数由HIV-1诱导产生的抗体在预防感染的起始或传播方面无效，因为它们要么不具有中和作用，要么具有狭窄的毒株特异性。已检测到罕见的“广谱中和”抗体，这些抗体可识别包膜糖蛋白上相对保守的区域。我们使用严格表征的、处于相关构象的三聚体HIV-1包膜蛋白均一制剂，分析了其中两种抗体2F5和4E10的中和分子机制。我们发现，它们在包膜蛋白胞外结构域的膜近端部分的表位，仅暴露于一种旨在模拟病毒进入过程中的中间状态的形式上。这些结果有助于解释2F5和4E10样抗体反应的罕见性，并提出了引发此类反应的策略。
