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方向正达尔文选择驱动进化对虫媒病毒登革热和寨卡病毒毒力和发病机制的影响。

Influence of directional positive Darwinian selection-driven evolution on arboviruses Dengue and Zika virulence and pathogenesis.

机构信息

Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (FIOCRUZ), Recife, PE 50740-465, Brazil.

Veterinary Virology and Animal Viral Diseases, Department of Infectious and Parasitic Diseases, FARAH Research Centre, Faculty of Veterinary Medicine, University of Liège, Belgium.

出版信息

Mol Phylogenet Evol. 2019 Nov;140:106607. doi: 10.1016/j.ympev.2019.106607. Epub 2019 Aug 29.

DOI:10.1016/j.ympev.2019.106607
PMID:31473337
Abstract

Dengue (DENV) and Zika (ZIKV) viruses are antigenically and evolutionarily related; immunological cross-reactions between them have been associated to both cross-protection and infection-enhanced mechanisms. Here, DENV-1-4 and ZIKV were investigated through Bayesian coalescent-based approaches and selection-driven Darwinian evolution methods using robust datasets. Our findings show that both DENV and ZIKV, driven essentially by directional positive selection, have undergone evolution and diversification and that their entire polyproteins are subject to an intense directional evolution. Interestingly, positively selected codons mapped here are directly associated to DENV-1-2 virulence as well as the ZIKV burgeoning 2015-16 outbreak in the Americas, therefore, having impact on the pathogenesis of these viruses. Biochemical prediction analysis focusing on markers involved in virulence and viral transmission dynamics identified alterations in N-Glycosylation-, Phosphorylation- and Palmitoylation-sites in ZIKV sampled from different countries, hosts and isolation sources. Taking into account both DENV-ZIKV co-circulation either into and/or out of flavivirus-endemic regions, as well as recombination and quasispecies scenarios, these results indicate the action of a selection-driven evolution affecting the biology, virulence and pathogenesis of these pathogens in a non-randomized environment.

摘要

登革热(DENV)和寨卡(ZIKV)病毒在抗原性和进化上具有相关性;它们之间的免疫交叉反应与交叉保护和感染增强机制有关。在这里,使用稳健的数据集,通过基于贝叶斯系统发育的方法和选择驱动的达尔文进化方法对 DENV-1-4 和 ZIKV 进行了研究。我们的研究结果表明,DENV 和 ZIKV 主要受到定向正选择的驱动,经历了进化和多样化,它们的整个多蛋白都受到强烈的定向进化的影响。有趣的是,这里映射的正选择密码子直接与 DENV-1-2 的毒力以及 ZIKV 在 2015-16 年在美洲的新兴爆发有关,因此,对这些病毒的发病机制有影响。针对与病毒毒力和病毒传播动力学相关的标记物的生化预测分析,鉴定了来自不同国家、宿主和分离源的 ZIKV 中的 N-糖基化、磷酸化和棕榈酰化位点的改变。考虑到 DENV-ZIKV 在黄病毒流行地区的同时传播,以及重组和准种情况,这些结果表明选择驱动的进化作用影响了这些病原体的生物学、毒力和发病机制,这种进化不是随机的。

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