在治疗后的控制器中,抗-V1/V3-甘氨酸广泛用于HIV-1中和抗体
Luis M Molinos-Albert1, Eduard Baquero2, Mélanie Bouvin-Pley3
1Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, INSERM U1222, Paris 75015, France.
Cell host & microbe
|July 11, 2023
概括
广泛中和抗体 (bNAbs) 可以帮助控制非抗逆转录病毒治疗 (ART) 的人群的HIV-1. 在后处理控制器 (PTC) 中识别的特定bNAb系针对一个关键的HIV-1包膜区域,有助于病毒控制.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 广泛中和HIV-1抗体 (bNAbs) 可以降低病毒载量,但往往无法对抗正在演变的自身病毒.
- 在未接受抗逆转录病毒治疗 (ART) 的人群中,bNAbs可能在自然控制HIV-1中发挥作用.
研究的目的:
- 描述一个bNAb B细胞系从具有广泛的血清中和能力的治疗后控制器 (PTC).
- 描述由来自该系的代表性抗体 (EPTC112) 准的表位.
- 了解bNAbs在控制ART以外的HIV-1感染中的作用.
主要方法:
- 来自治疗后控制器 (PTC) 的bNAb B细胞系的表征.
- 使用冷电子显微镜 (cryo-EM) 对抗体-抗原复合物的结构分析.
- 在HIV-1包膜剪切器上对抗体EPTC112的Epitope映射.
主要成果:
- 在PTC中确定了一种表现出广泛血清中和的bNAb血统.
- 抗体EPTC112针对HIV-1包膜糖蛋白的甘氨酸-V3循环超位中的四级表位.
- 低温EM检测显示EPTC112与N-甘氨酸 (N301,N156) 和V3循环 (GDIR327动机) 的相互作用.
- 与PTC同时存在的病毒对EPTC112具有耐药性,但被自身血IgG.G.中和.
结论:
- 交叉中和抗体可以影响PTC中的HIV-1感染动态.
- bNAbs可能有助于非ART患者的病毒控制,支持功能性HIV-1治愈策略.
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