Andrews Bryan, Fields Stanley
Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
ISME J. 2021 Aug;15(8):2195-2205. doi: 10.1038/s41396-021-00912-2. Epub 2021 Feb 15.
As hosts acquire resistance to viruses, viruses must overcome that resistance to re-establish infectivity, or go extinct. Despite the significant hurdles associated with adapting to a resistant host, viruses are evolutionarily successful and maintain stable coevolutionary relationships with their hosts. To investigate the factors underlying how pathogens adapt to their hosts, we performed a deep mutational scan of the region of the λ tail fiber tip protein that mediates contact with the receptor on λ's host, Escherichia coli. Phages harboring amino acid substitutions were subjected to selection for infectivity on wild type E. coli, revealing a highly restrictive fitness landscape, in which most substitutions completely abrogate function. A subset of positions that are tolerant of mutation in this assay, but diverse over evolutionary time, are associated with host range expansion. Imposing selection for phage infectivity on three λ-resistant hosts, each harboring a different missense mutation in the λ receptor, reveals hundreds of adaptive variants in λ. We distinguish λ variants that confer promiscuity, a general ability to overcome host resistance, from those that drive host-specific infectivity. Both processes may be important in driving adaptation to a novel host.
随着宿主获得对病毒的抗性，病毒必须克服这种抗性以重新建立感染性，否则就会灭绝。尽管在适应抗性宿主方面存在重大障碍，但病毒在进化上是成功的，并与宿主保持着稳定的共同进化关系。为了研究病原体适应宿主的潜在因素，我们对λ尾纤维尖端蛋白中与λ宿主大肠杆菌上的受体介导接触的区域进行了深度突变扫描。携带氨基酸替代的噬菌体在野生型大肠杆菌上进行感染性选择，揭示了一个高度受限的适应性景观，其中大多数替代完全消除了功能。在该实验中耐受突变但在进化时间上具有多样性的一部分位置与宿主范围扩展相关。对三种对λ具有抗性的宿主（每种宿主在λ受体中携带不同的错义突变）进行噬菌体感染性选择，揭示了λ中的数百种适应性变体。我们区分了赋予通用性（即克服宿主抗性的一般能力）的λ变体和驱动宿主特异性感染性的λ变体。这两个过程在推动对新宿主的适应中可能都很重要。
