Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from Recife, Brazil

Claire L. Donald(MRC University of Glasgow Centre for Virus Research), Benjamin Brennan(MRC University of Glasgow Centre for Virus Research), Stephanie L. Cumberworth(MRC University of Glasgow Centre for Virus Research), Veronica V. Rezelj(MRC University of Glasgow Centre for Virus Research), Jordan J. Clark(MRC University of Glasgow Centre for Virus Research), Marli Tenório Cordeiro(Fundação Oswaldo Cruz), Rafael Freitas de Oliveira França(Fundação Oswaldo Cruz), Lindomar Pena(Fundação Oswaldo Cruz), Gavin S. Wilkie(MRC University of Glasgow Centre for Virus Research), Ana da Silva Filipe(MRC University of Glasgow Centre for Virus Research), Christopher Davis(MRC University of Glasgow Centre for Virus Research), Joseph Hughes(MRC University of Glasgow Centre for Virus Research), Margus Varjak(MRC University of Glasgow Centre for Virus Research), Martin Selinger(Czech Academy of Sciences, Biology Centre), Luíza Zuvanov(MRC University of Glasgow Centre for Virus Research), Ania M. Owsianka(MRC University of Glasgow Centre for Virus Research), Arvind H. Patel(MRC University of Glasgow Centre for Virus Research), John McLauchlan(MRC University of Glasgow Centre for Virus Research), Brett D. Lindenbach(Yale University), Gamou Fall(Institut Pasteur de Dakar), Amadou A. Sall(Institut Pasteur de Dakar), Roman Biek(University of Glasgow), Jan Rehwinkel(MRC Human Immunology Unit), Esther Schnettler(MRC University of Glasgow Centre for Virus Research), Alain Kohl(MRC University of Glasgow Centre for Virus Research)
PLoS neglected tropical diseases
October 5, 2016
Cited by 250Open Access
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Abstract

BACKGROUND: 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.


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