Complete mapping of viral escape from neutralizing antibodies
Complete mapping of viral escape from neutralizing antibodies
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DOI：
10.1371/journal.ppat.1006271
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发表时间：
2017-03-01
期刊：
影响因子：
6.7
通讯作者：
Bloom, Jesse D.
中科院分区：
文献类型：
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作者：
Doud, Michael B.;Hensley, Scott E.;Bloom, Jesse D.
识别能够逃避抗体的病毒突变对于理解免疫和病毒进化之间的相互作用至关重要。我们描述了一种高通量方法来量化单克隆抗体对病毒蛋白的所有单个氨基酸突变的选择。这种方法，即突变抗原分析，涉及创建病毒的所有具有复制能力的蛋白质变体，用抗体进行选择，并使用深度测序来识别富集的突变。我们使用突变抗原分析来全面识别使流感病毒能够逃脱四种针对血凝素的单克隆抗体的突变，并通过中和测定验证关键发现。我们在抗体逃逸中发现了显着的突变水平特性：例如，在两种抗体靶向的单个残基上，一些突变逃脱了两种抗体，而其他突变仅逃脱了其中一种。由于突变抗原图谱可以快速绘制抗体选择的所有突变图谱，因此它对于阐明免疫特异性和解释病毒遗传变异的抗原后果非常有用。
Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.