MRC-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom.
Fundação Oswaldo Cruz-PE/Centro de Pesquisas Aggeu Magalhães, Departamento de Virologia, Campus da UFPE-Cidade Universitária, Recife/PE, Brasil.
PLoS Negl Trop Dis. 2016 Oct 5;10(10):e0005048. doi: 10.1371/journal.pntd.0005048. eCollection 2016 Oct.
The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions.
METHODOLOGY/PRINCIPAL FINDINGS: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action.
CONCLUSIONS/SIGNIFICANCE: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions.
寨卡病毒(ZIKV)在美洲的爆发,使原本鲜为人知的黄病毒科蚊媒传播的虫媒病毒,成为一个主要的公共卫生关注点。目前,人们对 ZIKV 的进化和生物学特性以及导致相关发病机制的因素知之甚少。确定临床病毒分离株的基因组序列并对这些序列中的元件进行特征描述,是深入了解病毒复制过程和病毒-宿主相互作用的重要前提。
方法/主要发现:我们从出现典型寨卡病毒相关症状的患者中获得了一株 ZIKV 分离株,利用高通量测序和其他分子生物学方法确定了其全长基因组序列,包括非编码区。对基因组区域进行了特征描述,并与其他可用分离株的序列进行了比较。此外,我们在感染 ZIKV 的细胞中鉴定出一种亚基因组黄病毒 RNA(sfRNA),它对 RIG-I 诱导的 I 型干扰素诱导具有拮抗活性,对 MDA-5 介导的作用的影响较小。
结论/意义:来自具有典型症状的患者的南美 ZIKV 分离株的全长基因组序列(包括非编码区),将支持为该病毒开发遗传工具的努力。检测到 sfRNA 可拮抗干扰素反应,这可能对进一步了解发病机制和病毒-宿主相互作用很重要。