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基孔肯雅病毒加勒比地区疫情的全基因组测序分析揭示了新的进化基因组元件。

Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements.

作者信息

Stapleford Kenneth A, Moratorio Gonzalo, Henningsson Rasmus, Chen Rubing, Matheus Séverine, Enfissi Antoine, Weissglas-Volkov Daphna, Isakov Ofer, Blanc Hervé, Mounce Bryan C, Dupont-Rouzeyrol Myrielle, Shomron Noam, Weaver Scott, Fontes Magnus, Rousset Dominique, Vignuzzi Marco

机构信息

Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Viral Populations and Pathogenesis Unit, Paris, France.

Institut Pasteur, International Group for Data Analysis, Paris, France.

出版信息

PLoS Negl Trop Dis. 2016 Jan 25;10(1):e0004402. doi: 10.1371/journal.pntd.0004402. eCollection 2016 Jan.

Abstract

BACKGROUND

Chikungunya virus (CHIKV), an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak.

METHODOLOGY/PRINCIPLE FINDINGS: We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3' untranslated region (UTR) structure, not previously found in nature, that led to increased replication in insect cells.

CONCLUSIONS/SIGNIFICANCE: Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3'UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naïve population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV.

摘要

背景

基孔肯雅病毒(CHIKV)是一种甲病毒,属于披膜病毒科,能够在人类中引起严重的发热疾病。2013年12月,CHIKV亚洲谱系从旧世界传播到美洲,并在新世界迅速蔓延。鉴于这种病毒在易感人群中的新出现,我们研究了感染个体中存在的病毒遗传多样性,以了解CHIKV在此次持续爆发期间可能是如何进化的。

方法/主要发现:我们使用深度测序技术结合成熟的生物信息学流程,对来自瓜德罗普岛和马提尼克岛(疫情中心的两个岛屿)的CHIKV感染个体中存在的少数变异体和多样性进行了表征。我们观察到了共有序列的变化以及人群中不同水平存在的多种少数变异体。此外,我们发现病毒在细胞系中单次传代后总体多样性显著降低。最后,我们从此次疫情中构建了一个感染性克隆,并鉴定出一种自然界中以前未发现的新型3'非翻译区(UTR)结构,该结构导致在昆虫细胞中的复制增加。

结论/意义:在此,我们对加勒比地区新出现的CHIKV疫情进行了宿主内准种分析。我们鉴定出了感染个体中存在的新型变异体以及一种新的3'UTR结构,这表明CHIKV一旦进入这个易感人群,就在短时间内迅速进化。这些研究强调了随着疫情的发展,需要持续进行病毒多样性监测,以便了解CHIKV的进化潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363d/4726740/e84f19b9a879/pntd.0004402.g001.jpg

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