MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection

作者: Victor Emmanuel Viana Geddes , Anibal Silva de Oliveira , Amilcar Tanuri , Eurico Arruda , Marcelo Ribeiro-Alves

DOI: 10.1371/JOURNAL.PNTD.0006508

关键词: VirologymicroRNAGene expression profilingVirusOropouche virusStimulator of interferon genesBiologyRegulation of gene expressionInnate immune systemViral replication

摘要: Oropouche Virus is the etiological agent of an arbovirus febrile disease that affects thousands people and widespread throughout Central South American countries. Although isolated in 1950's, still there scarce information regarding virus biology its prevalence likely underestimated. In order to identify elucidate interactions with host cells factors increase understanding about biology, we performed microRNA (miRNA) target genes screening human hepatocarcinoma cell line HuH-7. Cellular miRNAs are short non-coding RNAs regulates gene expression post-transcriptionally play key roles several steps viral infections. The large scale RT-qPCR based found 13 differentially expressed infected cells. Further validation confirmed miR-217 miR-576-3p were 5.5 fold up-regulated at early stages infection (6 hours post-infection). Using bioinformatics pathway enrichment analysis, predicted cellular targets for miR-576-3p. Differential analysis RNA from 95 selected revealed involved innate immunity modulation, release neurological disorder outcomes. decapping protein 2 (DCP2), a previous known restriction factor bunyaviruses transcription, as candidate progressively down-regulated during infection. Our also showed activators immune response through IFN-β pathway, STING (Stimulator Interferon Genes) TRAF3 (TNF-Receptor Associated Factor 3), progress. Inhibition or restricts OROV replication, decreasing (up 8.3 fold) titer (3 fold). Finally, escape mediated increasing levels resulting partners TRAF3. We concluded stating present study, first Peribunyaviridae member, gives insights prospective pathways could help understand pathogenesis, suggesting escapes antiviral cognates miRNAs.

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