Widespread Reassortment Shapes the Evolution and Epidemiology of Bluetongue Virus following European Invasion.
Widespread Reassortment Shapes the Evolution and Epidemiology of Bluetongue Virus following European Invasion.
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DOI：
10.1371/journal.ppat.1005056
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发表时间：
2015-08
期刊：
影响因子：
6.7
通讯作者：
Mertens P
中科院分区：
文献类型：
--
作者：
Nomikou K;Hughes J;Wash R;Kellam P;Breard E;Zientara S;Palmarini M;Biek R;Mertens P
基因组片段重组过程中的基因交换是所有具有片段基因组的病毒进化变化的重要机制，但在许多情况下，对其频率和生物学后果缺乏详细的了解。我们对蓝舌病毒(BTV)在欧洲最近暴发期间的重新分类进行了全面评估，蓝舌病毒是一种全球重要的家畜虫媒病原体。对过去50年来该地区出现的属于不同BTV血清型的150多个分离株进行了全基因组序列的生成和分析。基于这个新的数据集，我们证实了重组是一个频繁的过程，在病毒的进化中发挥着重要的和持续的作用。我们发现在所有10个细分市场中都有重新分类的证据，但对任何特定细分市场都没有明显的偏见。然而，我们观察到在重新排序过程中，特定片段相互关联的相对频率存在偏差。这表明选择性限制可能是由单个蛋白质或基因组片段之间的功能关系以及全基因组上位性相互作用引起的。正向选择下的位点更有可能在新重组的病毒中经历氨基酸变化，这为重组后的适应动态提供了额外的证据。我们表明，最近在欧洲使用的减毒活疫苗一再与野毒株重新组合，导致它们的遗传型和潜在的表型变异性。BTV基因组在片段起源方面的高度可塑性表明，目前主要基于仅由单个基因组片段决定的血清型的分类方案是不够的。我们的工作强调了需要更好地了解BTV以及其他节段RNA病毒中重组的机制和流行病学后果。分段病毒的基因组被分成多个片段，可与高等生物的染色体相媲美。当同一物种的两个节段性病毒感染同一细胞时，它们的后代可能包含从“亲代”病毒中提取的片段。这个过程被称为“重组”，代表了分段病毒进化的一种重要方式。虽然在某些节段病毒，特别是甲型流感病毒中，重组受到了很大的关注，但对其他大多数病毒，其频率和生物学后果仍然知之甚少。在这里，我们对蓝舌病毒的重组模式进行了全面的分析，蓝舌病毒是一种重要的家畜病原体，近几十年来在欧洲反复出现。我们证实了早先的报告，即重新排序是常见的，可能涉及来自用于控制疫情的活疫苗的片段。然而，病毒基因组的混合并不是严格随机的，在后代病毒中通常伴随着新的适应性变化。这指向了某些细分市场之间的重要功能链接(配对关联)。我们的发现对分段病毒的分类和控制具有重要意义，并对蓝舌病毒基因组不同部分之间的生物相互作用产生了新的见解和假设。
Genetic exchange by a process of genome-segment ‘reassortment’ represents an important mechanism for evolutionary change in all viruses with segmented genomes, yet in many cases a detailed understanding of its frequency and biological consequences is lacking. We provide a comprehensive assessment of reassortment in bluetongue virus (BTV), a globally important insect-borne pathogen of livestock, during recent outbreaks in Europe. Full-genome sequences were generated and analysed for over 150 isolates belonging to the different BTV serotypes that have emerged in the region over the last 5 decades. Based on this novel dataset we confirm that reassortment is a frequent process that plays an important and on-going role in evolution of the virus. We found evidence for reassortment in all ten segments without a significant bias towards any particular segment. However, we observed biases in the relative frequency at which particular segments were associated with each other during reassortment. This points to selective constraints possibly caused by functional relationships between individual proteins or genome segments and genome-wide epistatic interactions. Sites under positive selection were more likely to undergo amino acid changes in newly reassorted viruses, providing additional evidence for adaptive dynamics as a consequence of reassortment. We show that the live attenuated vaccines recently used in Europe have repeatedly reassorted with field strains, contributing to their genotypic, and potentially phenotypic, variability. The high degree of plasticity seen in the BTV genome in terms of segment origin suggests that current classification schemes that are based primarily on serotype, which is determined by only a single genome segment, are inadequate. Our work highlights the need for a better understanding of the mechanisms and epidemiological consequences of reassortment in BTV, as well as other segmented RNA viruses. Segmented viruses have genomes that are separated into multiple segments, comparable to chromosomes in higher organisms. When two segmented viruses of the same species infect the same cell, their progeny may incorporate segments picked up from the “parental” viruses. This process is called “reassortment” and represents an important way for segmented viruses to evolve. Whereas reassortment has received a lot of attention in certain segmented viruses, especially influenza A, its frequency and biological consequences remain poorly understood for most of the others. Here, we present a comprehensive analysis of the reassortment patterns in bluetongue virus, an important pathogen of livestock, during its repeated emergence in Europe in recent decades. We confirm earlier reports that reassortment is common and can involve segments derived from live vaccines used to control outbreaks. However, the mixing of viral genomes is not strictly random and reassortment is commonly followed by novel adaptive changes in the progeny virus. This points to important functional links (paired associations) between certain segments. Our findings have important implications for the classification and control of segmented viruses and generate new insights and hypotheses about the biological interactions among different parts of the bluetongue virus genome.