HIV 逃避 CCR5 单克隆抗体的新机制：表位转换。
Epitope switching as a novel escape mechanism of HIV to CCR5 monoclonal antibodies.
机构信息
Roche Palo Alto LLC, 3431 Hillview Ave., Palo Alto, CA 94304, USA.
出版信息
Antimicrob Agents Chemother. 2010 Feb;54(2):734-41. doi: 10.1128/AAC.00841-09. Epub 2009 Dec 7.
In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that MAb3952-resistant virus strains preferentially use the N terminus of CCR5, while the wild-type viruses preferentially use ECL-2. We propose this switch in the CCR5 binding site as a novel mechanism of HIV resistance.
在传代实验中，我们分离出了对 MAb3952 具有耐药性的 HIV 株，该 MAb3952 是一种趋化因子（C-C 基序）受体 5（CCR5）单克隆抗体（MAb），可与 CCR5 的第二个细胞外结构域（细胞外环 2 [ECL-2]）结合。对 MAb3952 耐药的病毒仍然对 CCR5 具有亲嗜性，并且对第二种 ECL-2 特异性抗体具有交叉耐药性。令人惊讶的是，对 MAb3952 耐药的病毒对 RoAb13 更为敏感，RoAb13 是一种与 CCR5 N 端结合的 CCR5 抗体。使用 CCR5 受体突变体，我们表明 MAb3952 耐药病毒株优先使用 CCR5 的 N 端，而野生型病毒则优先使用 ECL-2。我们提出这种 CCR5 结合位点的转换是 HIV 耐药的一种新机制。
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