Journal Article

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

Brennan, Benjamin, Sall, Amadou A., Clark, Jordan J., Selinger, Martin, Kohl, Alain, Davis, Christopher, Donald, Claire L., Owsianka, Ania M., Pena, Lindomar J., Da Silva Filipe, Ana, Rehwinkel, Jan, Fall, Gamou, Zuvanov, Luíza, Freitas de Oliveira França, Rafael, McLauchlan, John, Cordeiro, Marli T., Cumberworth, Stephanie L., Rezelj, Veronica V., Varjak, Margus, Patel, Arvind H., Wilkie, Gavin S., Biek, Roman, Hughes, Joseph, Lindenbach, Brett D., Schnettler, Esther

2016

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: A549 Cells / Animals / Biology / Biology and Life Sciences / Brazil - epidemiology / Colleges & universities / DEAD Box Protein 58 - metabolism / Disease Outbreaks / Genetic aspects / Genome, Viral / Genomes / High-Throughput Nucleotide Sequencing / Host-Pathogen Interactions / Humans / Interferon Type I - antagonists & inhibitors / Interferon Type I - biosynthesis / Interferon Type I - genetics / Medicine / Medicine and Health Sciences / Molecular biology / Mutation / Pathogenesis / Phylogeny / Physiological aspects / Public health / Research and analysis methods / RNA, Viral - genetics / RNA, Viral - isolation & purification / Tropical diseases / Vector-borne diseases / Vero Cells / Viral genetics / Virus Replication / Zika virus / Zika Virus - genetics / Zika Virus - isolation & purification / Zika Virus - pathogenicity / Zika Virus - physiology / Zika Virus Infection - virology