Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cell Rep. 2020 Apr 28;31(4):107587. doi: 10.1016/j.celrep.2020.107587.
Host genetic factors play a fundamental role in regulating humoral immunity to viral infection, including influenza A virus (IAV). Here, we utilize the Collaborative Cross (CC), a mouse genetic reference population, to study genetic regulation of variation in antibody response following IAV infection. CC mice show significant heritable variation in the magnitude, kinetics, and composition of IAV-specific antibody response. We map 23 genetic loci associated with this variation. Analysis of a subset of these loci finds that they broadly affect the antibody response to IAV as well as other viruses. Candidate genes are identified based on predicted variant consequences and haplotype-specific expression patterns, and several show overlap with genes identified in human mapping studies. These findings demonstrate that the host antibody response to IAV infection is under complex genetic control and highlight the utility of the CC in modeling and identifying genetic factors with translational relevance to human health and disease.
宿主遗传因素在调节针对病毒感染的体液免疫中起着至关重要的作用，包括甲型流感病毒（IAV）。在这里，我们利用合作杂交（CC），一种老鼠遗传参考群体，研究遗传调控在 IAV 感染后抗体反应的变化。CC 小鼠在 IAV 特异性抗体反应的幅度、动力学和组成方面表现出显著的可遗传性变异。我们对与这种变异相关的 23 个遗传位点进行了定位。对这些位点的一部分进行分析发现，它们广泛影响对 IAV 以及其他病毒的抗体反应。根据预测的变异后果和单倍型特异性表达模式确定候选基因，其中一些与人类图谱研究中确定的基因重叠。这些发现表明，宿主对 IAV 感染的抗体反应受到复杂的遗传控制，并突出了 CC 在模拟和确定对人类健康和疾病具有转化相关性的遗传因素方面的应用。
