The mutational variety of the live-attenuated influenza vaccine proteome
The mutational variety of the live-attenuated influenza vaccine proteome
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减毒流感疫苗蛋白质组的突变多样性
DOI：
10.1099/acmi.ac2021.po0409
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发表时间：
2022
影响因子：
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通讯作者：
McConnell M
中科院分区：
文献类型：
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作者：
McConnell M
流感病毒进化迅速，因此流感疫苗需要每年更新。因此，重要的是要确定新的突变可以容忍。为了评估这一点，我们询问了通过正确折叠、运输和组装成流感病毒颗粒而通过质量检查的蛋白质中可以鉴定出哪些突变。我们重新分析了从基因上明确定义的疫苗株的病毒颗粒中获得的质谱蛋白质组学数据，并确定了病毒蛋白质内的点突变。在甲型和B型流感病毒的蛋白质（包括HA、NA、M1、NP、NS1、PA和PB 2）中，以可观的频率在病毒颗粒中耐受点突变。结构分析用于评估这种蛋白质多样性对病毒分子生物学的可能影响。正如预期的那样，病毒颗粒耐受的突变通常发生在预期不会干扰蛋白质功能的位点。我们认为，使用蛋白质组学来确定病毒蛋白中可以或不能耐受突变的位点，可以通过突出具有抗原漂移潜力的区域来告知流感疫苗的开发。
Influenza viruses evolve rapidly, and for this reason the influenza vaccine needs to be updated every year. It is therefore important to identify where new mutations could be tolerated. To assess this, we asked which mutations could be identified in the proteins that had passed quality checks by being correctly folded, transported and assembled into influenza virus particles. We re-analysed mass spectrometry proteomics data obtained from the virus particles of genetically well-defined vaccine strains and identified point mutations within viral proteins. Point mutations were tolerated in virus particles at appreciable frequencies in proteins of both influenza A and B viruses, including HA, NA, M1, NP, NS1, PA and PB2. Structural analyses were used to assess the likely impact of this protein diversity on the molecular biology of the virus. As would be expected, mutations that were tolerated the virus particle generally occurred at sites that would not be expected to perturb protein function. We suggest that using proteomics to identify sites in viral proteins that either can or cannot tolerate mutations could inform influenza vaccine development by highlighting areas that have the potential for antigenic drift.