Static and Evolving Norovirus Genotypes: Implications for Epidemiology and Immunity.
Static and Evolving Norovirus Genotypes: Implications for Epidemiology and Immunity.
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DOI：
10.1371/journal.ppat.1006136
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发表时间：
2017-01
期刊：
影响因子：
6.7
通讯作者：
Green KY
中科院分区：
文献类型：
--
作者：
Parra GI;Squires RB;Karangwa CK;Johnson JA;Lepore CJ;Sosnovtsev SV;Green KY
诺如病毒是世界范围内引起急性胃肠炎的主要病原体。它们的RNA基因组是多样的，两个主要的基因组（GI和GII）由至少28种与人类疾病相关的基因型组成。为了阐明诺如病毒多样性和进化的机制，我们使用了大规模的基因组学方法来分析人类诺如病毒序列。对代表大多数已知感染人类的GI和GII基因型的2000多个近全长ORF2序列进行比较，结果显示，除GII.4外，每个基因型内的不同基因型内变异数量有限（≤5）。非GII.4基因型由一个或多个基因型内变异体组成，每个变异体含有几十年来仅相差几个残基的菌株（保持“静态”），并且共循环，没有明确的流行病学模式。相比之下，GII.4基因型呈现了最大数量的变体（>10），其随着时间的推移而进化，具有明显的周期性变体替换模式。为了扩大我们对这两种多样化模式（“静态”与“进化”）的理解，我们使用NGS分析了在不同爆发环境中感染GII.4，GII.6或GII.17病毒的健康个体中的近全长诺如病毒基因组。GII.4病毒在宿主内和宿主之间迅速积累突变，而GII.6和GII.17病毒保持相对稳定，这与其多样化模式一致。对遗传关系和自然历史模式的进一步分析发现，某些基因型被分组为更大的相关簇，在这里被指定为“免疫型”。我们提出，“免疫型”和它们的进化模式会影响特定诺如病毒基因型在人群中的流行。目前正在努力开发针对诺如病毒的疫苗，诺如病毒是急性胃肠炎的主要原因。我们研究的目的是了解不同基因型的诺如病毒株在人群中传播时如何进化和适应。利用我们实验室开发的大规模基因组学和计算工具，我们确定了诺如病毒基因型之间两种截然不同的进化模式：“静态”和“进化”。我们在这些进化模式的背景下从感染和爆发研究中挖掘了大型数据集，并提出了一种新的诺如病毒基因型抗原聚类模型，可以简化疫苗设计。
Noroviruses are major pathogens associated with acute gastroenteritis worldwide. Their RNA genomes are diverse, with two major genogroups (GI and GII) comprised of at least 28 genotypes associated with human disease. To elucidate mechanisms underlying norovirus diversity and evolution, we used a large-scale genomics approach to analyze human norovirus sequences. Comparison of over 2000 nearly full-length ORF2 sequences representing most of the known GI and GII genotypes infecting humans showed a limited number (≤5) of distinct intra-genotypic variants within each genotype, with the exception of GII.4. The non-GII.4 genotypes were comprised of one or more intra-genotypic variants, with each variant containing strains that differed by only a few residues over several decades (remaining “static”) and that have co-circulated with no clear epidemiologic pattern. In contrast, the GII.4 genotype presented the largest number of variants (>10) that have evolved over time with a clear pattern of periodic variant replacement. To expand our understanding of these two patterns of diversification (“static” versus “evolving”), we analyzed using NGS the nearly full-length norovirus genome in healthy individuals infected with GII.4, GII.6 or GII.17 viruses in different outbreak settings. The GII.4 viruses accumulated mutations rapidly within and between hosts, while the GII.6 and GII.17 viruses remained relatively stable, consistent with their diversification patterns. Further analysis of genetic relationships and natural history patterns identified groupings of certain genotypes into larger related clusters designated here as “immunotypes”. We propose that “immunotypes” and their evolutionary patterns influence the prevalence of a particular norovirus genotype in the human population. Efforts are underway to develop vaccines against norovirus, a leading cause of acute gastroenteritis. The purpose of our study was to understand how norovirus strains within different genotypes evolve and adapt as they are transmitted in the human population. Using large-scale genomics and computational tools developed in our laboratory, we identified two strikingly different evolutionary patterns among norovirus genotypes: “static” and “evolving.” We mined large datasets from infection and outbreak studies in context of these evolutionary patterns and propose a new model for antigenic clustering of norovirus genotypes that could simplify vaccine design.