Strottmann Daisy Maria, Zanluca Camila, Mosimann Ana Luiza Pamplona, Koishi Andrea C, Auwerter Nathalia Cavalheiro, Faoro Helisson, Cataneo Allan Henrique Depieri, Kuczera Diogo, Wowk Pryscilla Fanini, Bordignon Juliano, Duarte Dos Santos Claudia Nunes
Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Virologia Molecular, Curitiba, PR, Brasil.
Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Regulação da Expressão Gênica, Curitiba, PR, Brasil.
Mem Inst Oswaldo Cruz. 2019;114:e190150. doi: 10.1590/0074-02760190150. Epub 2019 Aug 19.
Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before. Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population. However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown.
The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics.
The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells.
Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified. Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness. The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells.
Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.
近期疫情中报告的寨卡病毒(ZIKV)感染与以前从未与寨卡病毒相关联的临床并发症有关。适应性突变可能促成了寨卡病毒成为对非免疫人群的全球健康威胁。然而,寨卡病毒基因决定因素、发病机制以及在拉丁美洲和加勒比地区的快速传播之间的因果关系仍然广泛未知。
本研究的目的是对2015/2016年巴西疫情期间从患者样本中获得的三株寨卡病毒分离株进行特征分析。
对这些毒株的寨卡病毒基因组进行了全序列测定,并在细胞系和人原代细胞中进行了体外感染动力学实验。
在三株巴西分离株的病毒基因组中鉴定出八个非同义替换。用哺乳动物细胞系A549、Huh7.5、Vero E6和人单核细胞衍生树突状细胞(mdDCs)以及昆虫细胞(Aag2、C6/36和AP61)进行了感染动力学实验,结果表明其中一些突变可能与不同的病毒适应性有关。与成熟的寨卡病毒株(MR766和PE243)相比,临床分离株在感染率上也存在差异,尤其是在感染哺乳动物细胞的能力方面。
对三株近期寨卡病毒分离株的基因组分析揭示了一些非同义替换,这些替换可能会影响病毒在哺乳动物和昆虫细胞中的适应性。