Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype.
Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype.
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DOI：
10.1371/journal.ppat.1004838
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发表时间：
2015-05
期刊：
影响因子：
6.7
通讯作者：
Vignuzzi M
中科院分区：
文献类型：
--
作者：
Bordería AV;Isakov O;Moratorio G;Henningsson R;Agüera-González S;Organtini L;Gnädig NF;Blanc H;Alcover A;Hafenstein S;Fontes M;Shomron N;Vignuzzi M
了解病原体如何定植和适应新的宿主环境是研究新兴传染病的主要目标。适应性突变出现在RNA病毒感染期间产生的数千种变体中，识别这些变体将揭示向性和物种跳跃的变化如何发生。在这里，我们使科萨基B3病毒适应于高许可和低许可的环境。使用深度测序和生物信息学，我们确定了一个多步骤的适应性过程，涉及受体足迹中的残基，这些残基与受体可用性相关，并以环境特异性方式增加病毒适应性。我们发现，适应发生的选择一个显性突变，然后由少数变异群体的选择，共同赋予的健身增加观察到的人口，而不是选择一个单一的显性基因型。当RNA病毒复制时，它们的错误率很高;因此，它们的种群不是由单一的基因型组成，而是由一群不同但相关的基因组组成。这种突变谱被描述为病毒准种，其组成对进化、适应和出现具有重要影响。在这项研究中，由于使用深度测序，我们详细分析了适应性，并确定了模型RNA病毒柯萨奇病毒B3对新环境A549细胞的适应途径。我们的研究结果表明，适应发生在新的细胞环境中的病毒受体的差异表达，相比前者。我们的实验和数学分析表明，适应性的相应增加是由一组基因型（包括低频变异）的选择和贡献造成的，而不是由单一的显性基因组造成的。我们的工作强调了在研究RNA病毒生物学和进化时考虑群体效应的重要性。
Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases. Adaptive mutations arise among the thousands of variants generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly permissive and less permissive environment. Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner. We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype. When RNA viruses replicate, they do so with a high rate of error; hence, their populations are not composed of a single genotype, but of a swarm of different, yet related, genomes. This mutant spectrum has been described as the viral quasispecies, and its composition has important consequences for evolution, adaptation and emergence. In this study, we analysed adaptation in fine detail thanks to the use of the deep sequencing, and we determined the adaptative pathway of a model RNA virus, Coxsackievirus B3, to a new environment, A549 cells. Our results demonstrate that adaptation occurred in response to a differential expression of the virus receptors in the new cellular environment, compared to the former. Our experiments and mathematical analyses established that the corresponding increase in fitness resulted from the selection and contribution of a group of genotypes, including low frequency variants, and not to the effect of a single, dominant genome. Our work underscores the importance of considering group effects when studying RNA virus biology and evolution.
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影响因子：
64.8
作者：
Burch, CL;Chao, L
通讯作者：
Chao, L
影响因子：
5.4
作者：
Hafenstein, Susan;Bowman, Valorie D.;Rossmann, Michael G.
通讯作者：
Rossmann, Michael G.
DOI：
10.2174/138620709789104915
发表时间：
2009-09-01
影响因子：
1.8
作者：
Concepcion, Joy;Witte, Krista;Tan, Hong
通讯作者：
Tan, Hong
影响因子：
64.8
作者：
Imai, Masaki;Watanabe, Tokiko;Hatta, Masato;Das, Subash C.;Ozawa, Makoto;Shinya, Kyoko;Zhong, Gongxun;Hanson, Anthony;Katsura, Hiroaki;Watanabe, Shinji;Li, Chengjun;Kawakami, Eiryo;Yamada, Shinya;Kiso, Maki;Suzuki, Yasuo;Maher, Eileen A.;Neumann, Gabriele;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
影响因子：
64.5
作者：
Coyne, CB;Bergelson, JM
通讯作者：
Bergelson, JM