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

dc.creatorTorres, Maria Celeste
dc.creatorKarl, Ana Luiza Martins
dc.creatorSilva, Matheus Müller Pereira da
dc.creatorDardenne, Laurent Emmanuel
dc.creatorFilippis, Ana Maria Bispo de
dc.date2022-02-09T16:44:33Z
dc.date2022-02-09T16:44:33Z
dc.date2021
dc.date.accessioned2023-09-26T20:12:42Z
dc.date.available2023-09-26T20:12:42Z
dc.identifierTORRES, 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.identifier2165-0497
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/51113
dc.identifier10.1128/Spectrum.00256-21
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8851493
dc.descriptionIntrahost 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectAnálise in silico
dc.subjectMutações do sorotipo 2 do vírus da dengue
dc.subjectDetectado no Nível Intrahost
dc.subjectPacientes
dc.subjectDiferentes Resultados clínicos
dc.subjectIn Silico Analysis
dc.subjectDengue Virus Serotype 2 Mutations
dc.subjectDetected
dc.subjectIntrahost Level
dc.subjectPatients
dc.subjectDifferent Clinical Outcomes
dc.titleIn Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes
dc.typeArticle


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