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

Detalhes bibliográficos
Autor(a) principal: Geddes, Victor Emmanuel Viana
Data de Publicação: 2018
Outros Autores: Oliveira, Anibal Silva de, Tanuri, Amilcar, Arruda, Eurico, Ribeiro-Alves, Marcelo, Aguiar, Renato Santana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/33950
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.
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spelling Geddes, Victor Emmanuel VianaOliveira, Anibal Silva deTanuri, AmilcarArruda, EuricoRibeiro-Alves, MarceloAguiar, Renato Santana2019-07-10T14:56:46Z2019-07-10T14:56:46Z2018GEDDES, Victor Emmanuel Viana et al. MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection. PLos Neglected Tropical Diseases, p. 1-25, May 2018.1935-2727https://www.arca.fiocruz.br/handle/icict/3395010.1371/journal.pntd.00065081935-2735engPublic Library of ScienceMicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Virologia. Departamento de Biologia Celular e Molecular. Ribeirão Preto, SP, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Centro de Pesquisa em Virologia. Departamento de Biologia Celular e Molecular. Ribeirão Preto, SP, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Oropouche Virus is the etiological agent of an arbovirus febrile disease that affects thousands of people and is widespread throughout Central and South American countries. Although isolated in 1950's, still there is scarce information regarding the virus biology and its prevalence is likely underestimated. In order to identify and elucidate interactions with host cells factors and increase the understanding about the Oropouche Virus biology, we performed microRNA (miRNA) and target genes screening in human hepatocarcinoma cell line HuH-7. Cellular miRNAs are short non-coding RNAs that regulates gene expression post-transcriptionally and play key roles in several steps of viral infections. The large scale RT-qPCR based screening found 13 differentially expressed miRNAs in Oropouche infected cells. Further validation confirmed that miR-217 and miR-576-3p were 5.5 fold up-regulated at early stages of virus infection (6 hours post-infection). Using bioinformatics and pathway enrichment analysis, we predicted the cellular targets genes for miR-217 and miR-576-3p. Differential expression analysis of RNA from 95 selected targets revealed genes involved in innate immunity modulation, viral release and neurological disorder outcomes. Further analysis revealed the gene of decapping protein 2 (DCP2), a previous known restriction factor for bunyaviruses transcription, as a miR-217 candidate target that is progressively down-regulated during Oropouche infection. Our analysis also showed that activators genes involved in innate immune response through IFN-β pathway, as STING (Stimulator of Interferon Genes) and TRAF3 (TNF-Receptor Associated Factor 3), were down-regulated as the infection progress. Inhibition of miR-217 or miR-576-3p restricts OROV replication, decreasing viral RNA (up to 8.3 fold) and virus titer (3 fold). Finally, we showed that virus escape IFN-β mediated immune response increasing the levels of cellular miR-576-3p resulting in a decreasing of its partners STING and TRAF3. We concluded stating that the present study, the first for a Peribunyaviridae member, gives insights in its prospective pathways that could help to understand virus biology, interactions with host cells and pathogenesis, suggesting that the virus escapes the antiviral cellular pathways increasing the expression of cognates miRNAs.Oropouche infectionMicroRNAMiR-217MiR-576-3pinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83104https://www.arca.fiocruz.br/bitstream/icict/33950/1/license.txt79178e5f2a0eb066867a274556814938MD51ORIGINALve_Geddes_Victor_etal_INI_2018.pdfve_Geddes_Victor_etal_INI_2018.pdfapplication/pdf6355141https://www.arca.fiocruz.br/bitstream/icict/33950/2/ve_Geddes_Victor_etal_INI_2018.pdff827b2156dc1b64303671164443924c6MD52TEXTve_Geddes_Victor_etal_INI_2018.pdf.txtve_Geddes_Victor_etal_INI_2018.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
title MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
spellingShingle MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
Geddes, Victor Emmanuel Viana
Oropouche infection
MicroRNA
MiR-217
MiR-576-3p
title_short MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
title_full MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
title_fullStr MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
title_full_unstemmed MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
title_sort MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during oropouche infection
author Geddes, Victor Emmanuel Viana
author_facet Geddes, Victor Emmanuel Viana
Oliveira, Anibal Silva de
Tanuri, Amilcar
Arruda, Eurico
Ribeiro-Alves, Marcelo
Aguiar, Renato Santana
author_role author
author2 Oliveira, Anibal Silva de
Tanuri, Amilcar
Arruda, Eurico
Ribeiro-Alves, Marcelo
Aguiar, Renato Santana
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Geddes, Victor Emmanuel Viana
Oliveira, Anibal Silva de
Tanuri, Amilcar
Arruda, Eurico
Ribeiro-Alves, Marcelo
Aguiar, Renato Santana
dc.subject.en.pt_BR.fl_str_mv Oropouche infection
MicroRNA
MiR-217
MiR-576-3p
topic Oropouche infection
MicroRNA
MiR-217
MiR-576-3p
description Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Genética. Rio de Janeiro, RJ, Brasil.
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2019-07-10T14:56:46Z
dc.date.available.fl_str_mv 2019-07-10T14:56:46Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv GEDDES, Victor Emmanuel Viana et al. MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection. PLos Neglected Tropical Diseases, p. 1-25, May 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/33950
dc.identifier.issn.pt_BR.fl_str_mv 1935-2727
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0006508
dc.identifier.eissn.none.fl_str_mv 1935-2735
identifier_str_mv GEDDES, Victor Emmanuel Viana et al. MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection. PLos Neglected Tropical Diseases, p. 1-25, May 2018.
1935-2727
10.1371/journal.pntd.0006508
1935-2735
url https://www.arca.fiocruz.br/handle/icict/33950
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/33950/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/33950/2/ve_Geddes_Victor_etal_INI_2018.pdf
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