Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin
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DOI：
10.7554/elife.49324
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发表时间：
2019-08-27
期刊：
影响因子：
7.7
通讯作者：
Bloom, Jesse D.
中科院分区：
文献类型：
--
作者：
Lee, Juhye M.;Eguia, Rachel;Bloom, Jesse D.
一个长期存在的问题是，流感病毒是如何进化来逃避人类免疫的，人类免疫是多克隆的，可以针对许多不同的表位。在这里，我们描绘了流感主要表面蛋白的所有氨基酸突变如何影响多克隆人血清对病毒的中和作用。一些人的血清如此集中，以至于它选择了单一的突变，这些突变使病毒中和减少了一个数量级以上。然而，不同的病毒变异可以逃脱不同个体的血清。这种病毒逃逸突变的个体间变异在只感染过一次特定病毒株的雪貂中不存在。我们的结果表明，不同的单一突变如何帮助流感病毒逃避不同人类群体成员的免疫，这一现象可能会塑造病毒的进化和疾病的易感性。
A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza's major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.