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抗体抑制流感A病毒的组装和释放

He Yuanyuan^1,2, Guo Zijian^1,2, Sofie Subiaur^1,2

¹Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.

bioRxiv : the preprint server for biology

|August 23, 2023

概括

针对流感病毒的单克隆抗体 (mAbs) 可以阻止病毒的释放. 抗原交联是这种病毒退出抑制的关键,有助于治疗性抗体的发展.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
结构生物学结构生物学

背景情况:

抗体对于控制流感病毒感染至关重要.
单克隆抗体 (mAbs) 可以抑制流感病毒的聚集和释放,但这种机制的效力尚未完全理解.
从其他抗体功能中分离抑制病毒退出的效果是具有挑战性的.

研究的目的:

开发基于成像的试验,以量化mAbs在限制流感A病毒 (IAV) 输出方面的有效性.
调查抗原交联在抗体介导的病毒释放抑制中的作用.
探索针对不同IAV表面蛋白的抗体的多功能性.

主要方法:

开发基于成像的测定方法,以测量mAbs.的病毒退出抑制.
测试一系列针对血凝素 (HA),神经氨基酶 (NA) 和M2蛋白的mAbs.
使用基于结构的计算模型来分析抗原交联效应.

主要成果:

中和抗HA mAbs抑制病毒聚集和释放的度高于病毒进入抑制.
抗HA mAbs改变了病毒形态,减少了丝状颗粒的产生.
抗NA和抗M2mAbs也限制病毒的输出;抗NA抑制部分是由于酶活性的丧失.
抗原在受感染细胞或病毒/细胞膜上的交联对抑制至关重要.
实验和计算方法区分了不同的交联模式.

结论:

针对流感病毒表面蛋白的抗体表现出多功能性,抑制了输入和输出.
抗原交联是抗体介导的病毒释放限制的关键机制.
开发的框架有助于剖析抗体多功能性,以改善治疗性抗体和疫苗设计.

关键词:

流感病毒是流感病毒.抗体是一种抗体.交叉链接是指交叉链接.病毒组装组件病毒组件

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