In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes

Detalhes bibliográficos
Autor(a) principal: Torres, Maria Celeste
Data de Publicação: 2021
Outros Autores: Karl, Ana Luiza Martins, Silva, Matheus Müller Pereira da, Dardenne, Laurent Emmanuel, Filippis, Ana Maria Bispo de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/51113
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.
id CRUZ_c2142759041fea7c1dcdb8a4d6c64d5c
oai_identifier_str oai:www.arca.fiocruz.br:icict/51113
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Torres, Maria CelesteKarl, Ana Luiza MartinsSilva, Matheus Müller Pereira daDardenne, Laurent EmmanuelFilippis, Ana Maria Bispo de2022-02-09T16:44:33Z2022-02-09T16:44:33Z2021TORRES, Maria Celeste et al. In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes. Microbiology Spectrum, v. 9, n. 2, e00256-21, p. 1 - 29, Sept. 2021.2165-0497https://www.arca.fiocruz.br/handle/icict/5111310.1128/Spectrum.00256-21engAmerican Society for MicrobiologyAnálise in silicoMutações do sorotipo 2 do vírus da dengueDetectado no Nível IntrahostPacientesDiferentes Resultados clínicosIn Silico AnalysisDengue Virus Serotype 2 MutationsDetectedIntrahost LevelPatientsDifferent Clinical OutcomesIn Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Laboratório Nacional de Computação Científica. Grupo de Modelagem Molecular de Sistemas Biológicos. GMMSB/LNCC-MCTI, Petrópolis,, RJ, Brasil.Laboratório Nacional de Computação Científica. Grupo de Modelagem Molecular de Sistemas Biológicos. GMMSB/LNCC-MCTI, Petrópolis,, RJ, Brasil.Laboratório Nacional de Computação Científica. Grupo de Modelagem Molecular de Sistemas Biológicos. GMMSB/LNCC-MCTI, Petrópolis,, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Intrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it may also be linked to viral pathogenesis. Intending to shed light on the viral determinants for severe dengue pathogenesis, we previously analyzed the DENV-2 intrahost genetic diversity in 68 patients clinically classified as dengue fever (n = 31), dengue with warning signs (n = 19), and severe dengue (n = 18), performing viral whole-genome deep sequencing from clinical samples with an amplicon-free approach. From it, we identified a set of 141 relevant mutations distributed throughout the viral genome that deserved further attention. Therefore, we employed molecular modeling to recreate three-dimensional models of the viral proteins and secondary RNA structures to map the mutations and assess their potential effects. Results showed that, in general lines, disruptive variants were identified primarily among dengue fever cases. In contrast, potential immune-escape variants were associated mainly with warning signs and severe cases, in line with the latter’s longer intrahost evolution times. Furthermore, several mutations were located on protein-surface regions, with no associated function. They could represent sites of further investigation, as the interaction of viral and host proteins is critical for both host immunomodulation and virus hijacking of the cellular machinery. The present analysis provides new information about the implications of the intrahost genetic diversity of DENV-2, contributing to the knowledge about the viral factors possibly involved in its pathogenesis within the human host. Strengthening our results with functional studies could allow many of these variants to be considered in the design of therapeutic or prophylactic compounds and the improvement of diagnostic assays.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/51113/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAnamariaFilippis_MariaCeleste_etal_IOC_2021.pdfAnamariaFilippis_MariaCeleste_etal_IOC_2021.pdfapplication/pdf7475085https://www.arca.fiocruz.br/bitstream/icict/51113/2/AnamariaFilippis_MariaCeleste_etal_IOC_2021.pdf85fd0c43470901a05964c208f948751fMD52icict/511132022-06-24 13:12:32.566oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T16:12:32Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
title In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
spellingShingle In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
Torres, Maria Celeste
Análise in silico
Mutações do sorotipo 2 do vírus da dengue
Detectado no Nível Intrahost
Pacientes
Diferentes Resultados clínicos
In Silico Analysis
Dengue Virus Serotype 2 Mutations
Detected
Intrahost Level
Patients
Different Clinical Outcomes
title_short In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
title_full In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
title_fullStr In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
title_full_unstemmed In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
title_sort In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
author Torres, Maria Celeste
author_facet Torres, Maria Celeste
Karl, Ana Luiza Martins
Silva, Matheus Müller Pereira da
Dardenne, Laurent Emmanuel
Filippis, Ana Maria Bispo de
author_role author
author2 Karl, Ana Luiza Martins
Silva, Matheus Müller Pereira da
Dardenne, Laurent Emmanuel
Filippis, Ana Maria Bispo de
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Torres, Maria Celeste
Karl, Ana Luiza Martins
Silva, Matheus Müller Pereira da
Dardenne, Laurent Emmanuel
Filippis, Ana Maria Bispo de
dc.subject.other.pt_BR.fl_str_mv Análise in silico
Mutações do sorotipo 2 do vírus da dengue
Detectado no Nível Intrahost
Pacientes
Diferentes Resultados clínicos
topic Análise in silico
Mutações do sorotipo 2 do vírus da dengue
Detectado no Nível Intrahost
Pacientes
Diferentes Resultados clínicos
In Silico Analysis
Dengue Virus Serotype 2 Mutations
Detected
Intrahost Level
Patients
Different Clinical Outcomes
dc.subject.en.pt_BR.fl_str_mv In Silico Analysis
Dengue Virus Serotype 2 Mutations
Detected
Intrahost Level
Patients
Different Clinical Outcomes
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2022-02-09T16:44:33Z
dc.date.available.fl_str_mv 2022-02-09T16:44:33Z
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 TORRES, Maria Celeste et al. In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes. Microbiology Spectrum, v. 9, n. 2, e00256-21, p. 1 - 29, Sept. 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/51113
dc.identifier.issn.pt_BR.fl_str_mv 2165-0497
dc.identifier.doi.none.fl_str_mv 10.1128/Spectrum.00256-21
identifier_str_mv TORRES, Maria Celeste et al. In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes. Microbiology Spectrum, v. 9, n. 2, e00256-21, p. 1 - 29, Sept. 2021.
2165-0497
10.1128/Spectrum.00256-21
url https://www.arca.fiocruz.br/handle/icict/51113
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 American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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/51113/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/51113/2/AnamariaFilippis_MariaCeleste_etal_IOC_2021.pdf
bitstream.checksum.fl_str_mv 5a560609d32a3863062d77ff32785d58
85fd0c43470901a05964c208f948751f
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1813008853805039616

Registros relacionados