Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA; University of California, Berkeley/University of California, San Francisco Graduate Group in Bioengineering, Berkeley, CA 94720, USA; Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Cell. 2019 Jan 10;176(1-2):281-294.e19. doi: 10.1016/j.cell.2018.10.056. Epub 2018 Nov 29.
Influenza viruses inhabit a wide range of host environments using a limited repertoire of protein components. Unlike viruses with stereotyped shapes, influenza produces virions with significant morphological variability even within clonal populations. Whether this tendency to form pleiomorphic virions is coupled to compositional heterogeneity and whether it affects replicative fitness remains unclear. Here, we address these questions by developing a strain of influenza A virus amenable to rapid compositional characterization through quantitative, site-specific labeling of viral proteins. Using this strain, we find that influenza A produces virions with broad variations in size and composition from even single infected cells. This phenotypic variability contributes to virus survival during environmental challenges, including exposure to antivirals. Complementing genetic adaptations that act over larger populations and longer times, this "low-fidelity" assembly of influenza A virus allows small populations to survive environments that fluctuate over individual replication cycles.
流感病毒在广泛的宿主环境中使用有限的蛋白质组件。与具有定型形状的病毒不同，流感病毒即使在克隆种群中也能产生具有显著形态变异性的病毒粒子。这种形成多形病毒粒子的趋势是否与组成异质性相关，以及它是否影响复制适应性仍不清楚。在这里，我们通过开发一种流感 A 病毒株来解决这些问题，该病毒株可通过对病毒蛋白进行定量、定点标记来快速进行组成特征分析。使用这种菌株，我们发现即使来自单个感染细胞，流感 A 也能产生大小和组成广泛变化的病毒粒子。这种表型变异性有助于病毒在环境挑战（包括暴露于抗病毒药物）期间的存活。这种流感 A 病毒的“低保真度”组装补充了在更大种群和更长时间内起作用的遗传适应，使小种群能够在单个复制周期中波动的环境中存活。
