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

Abstract

BackgroundThe 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 findingsWe 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/SignificanceThe 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.

Knotty Zika Virus Blocks Exonuclease to Produce Subgenomic Flaviviral RNAs

“…For instance, the 3’UTRs of a number of mosquito-borne flaviviruses produce subgenomic flavivirus RNAs (sfRNAs) that regulate infection (Pijlman et al, 2008). Recently, Akiyama et al, (2016) found that these sfRNAs are produced in a number of cell types during ZIKV infection, supporting the recent findings of Donald et al (Akiyama et al, 2016; Donald et al, 2016). sfRNAs regulate the flaviviral life cycle and contribute to their pathogenicity by a number of mechanisms.…”

Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle

“…This would be in accordance with the findings for DENV, which indicated that certain RNA structure elements in the flavivirus 3′ UTR, like RNA structure duplications, play a role in host adaptation (37, 38). Furthermore, the flavivirus 3′ UTR is the origin of subgenomic flavivirus RNAs (sfRNAs) (39–41). It has been reported that sfRNAs exhibit interferon-antagonistic activities (41, 42).…”

“…Furthermore, the flavivirus 3′ UTR is the origin of subgenomic flavivirus RNAs (sfRNAs) (39–41). It has been reported that sfRNAs exhibit interferon-antagonistic activities (41, 42). In comparison to, e.g., wt West Nile virus, growth of a West Nile virus mutant deficient in producing sfRNA was reduced in wt mouse embryonic fibroblasts (MEFs), while the mutant replicated like the wt virus in IRF3 −/− × IRF7 −/− MEFs as well as in Vero and BHK cells, which are also described to be interferon deficient (39, 42, 43).…”

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

“…: NC012532.1, kindly provided by Dr. Davis Ferreira, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil) was isolated from a rhesus monkey and injected intracerebrally on Swiss mice for several passages [1] and ZIKV BR (Recife/Brazil, ZIKV PE/243, accession no: KX197192.1, kindly provided by Dr. Marli Tenório Cordeiro, Centro de Pesquisas Aggeu Magalhães, Recife, Brazil) was isolated from a patient presenting classical symptoms of ZIKV infection [28]. These viruses were propagated in Vero and C6/36 cells, respectively.…”