Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis

<b>Background:</b> In this study, we investigated the role of extracellular vesicles (EVs) in the pathogenesis of Congenital Zika Syndrome (CZS). Previous studies have highlighted the role of EVs in intercellular communication and the modulation of biological processes during viral infec...

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Main Authors: Leticia Gomes-de-Pontes, Lucila Akune Barreiros, Lillian Nunes Gomes, Ranieri Coelho Salgado, Sarah Maria da Silva Napoleão, Paulo V. Soeiro-Pereira, Saulo Duarte Passos, Antonio Condino-Neto
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Language:English
Published: MDPI AG 2024-12-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/1/32
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author Leticia Gomes-de-Pontes
Lucila Akune Barreiros
Lillian Nunes Gomes
Ranieri Coelho Salgado
Sarah Maria da Silva Napoleão
Paulo V. Soeiro-Pereira
Saulo Duarte Passos
Antonio Condino-Neto
author_facet Leticia Gomes-de-Pontes
Lucila Akune Barreiros
Lillian Nunes Gomes
Ranieri Coelho Salgado
Sarah Maria da Silva Napoleão
Paulo V. Soeiro-Pereira
Saulo Duarte Passos
Antonio Condino-Neto
author_sort Leticia Gomes-de-Pontes
collection DOAJ
description <b>Background:</b> In this study, we investigated the role of extracellular vesicles (EVs) in the pathogenesis of Congenital Zika Syndrome (CZS). Previous studies have highlighted the role of EVs in intercellular communication and the modulation of biological processes during viral infections, motivating our in-depth analysis. Our objective was to identify specific molecular signatures in the EVs of patients with CZS, focusing on their potential as biomarkers and on cellular pathways affected by the infection. <b>Methods:</b> We conducted advanced proteomic and metabolomic analyses using mass spectrometry for protein and metabolite identification. EVs were isolated from CZS patient samples and control groups using Izon qEV size-exclusion chromatography columns. <b>Results:</b> The analyzed EVs presented distinct molecular profiles in patients with CZS. Proteomic analysis revealed significant alterations in specific proteins, suggesting involvement in the PI3K-AKT-mTOR pathway, while metabolomics highlighted metabolites related to critical processes in Zika virus pathogenesis. These findings suggest a key role for the PI3K-AKT-mTOR pathway in regulating cellular processes during infection and indicate the involvement of EVs in intercellular communication. Additionally, the results identified potential biomarkers capable of aiding early diagnosis and assessing disease progression. <b>Conclusions:</b> This study demonstrates that EVs play a crucial role in intercellular communication during Zika virus infection. The identification of specific alterations in the PI3K-AKT-mTOR pathway highlights a possible therapeutic target, providing new opportunities for the development of more effective treatment strategies for CZS. Our findings significantly advance the understanding of CZS and underscore the need for further investigations using advanced techniques to validate and explore these potential molecular targets.
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spelling doaj-art-de2943509b7e4e94a51112441935de0a2025-01-24T13:24:55ZengMDPI AGBiomolecules2218-273X2024-12-011513210.3390/biom15010032Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic AnalysisLeticia Gomes-de-Pontes0Lucila Akune Barreiros1Lillian Nunes Gomes2Ranieri Coelho Salgado3Sarah Maria da Silva Napoleão4Paulo V. Soeiro-Pereira5Saulo Duarte Passos6Antonio Condino-Neto7Department of Immunology (LIH), Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415-Butantã, São Paulo 05508-000, SP, BrazilDepartment of Immunology (LIH), Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415-Butantã, São Paulo 05508-000, SP, BrazilDepartment of Immunology (LIH), Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415-Butantã, São Paulo 05508-000, SP, BrazilDepartment of Immunology (LIH), Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415-Butantã, São Paulo 05508-000, SP, BrazilDepartment of Immunology (LIH), Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415-Butantã, São Paulo 05508-000, SP, BrazilDepartment of Pathology, Federal University of Maranhão, São Luís 65065-545, MA, BrazilInfectious Pediatric Laboratory, Medicine School of Jundiaí, Jundiaí 13202-550, SP, BrazilDepartment of Immunology (LIH), Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415-Butantã, São Paulo 05508-000, SP, Brazil<b>Background:</b> In this study, we investigated the role of extracellular vesicles (EVs) in the pathogenesis of Congenital Zika Syndrome (CZS). Previous studies have highlighted the role of EVs in intercellular communication and the modulation of biological processes during viral infections, motivating our in-depth analysis. Our objective was to identify specific molecular signatures in the EVs of patients with CZS, focusing on their potential as biomarkers and on cellular pathways affected by the infection. <b>Methods:</b> We conducted advanced proteomic and metabolomic analyses using mass spectrometry for protein and metabolite identification. EVs were isolated from CZS patient samples and control groups using Izon qEV size-exclusion chromatography columns. <b>Results:</b> The analyzed EVs presented distinct molecular profiles in patients with CZS. Proteomic analysis revealed significant alterations in specific proteins, suggesting involvement in the PI3K-AKT-mTOR pathway, while metabolomics highlighted metabolites related to critical processes in Zika virus pathogenesis. These findings suggest a key role for the PI3K-AKT-mTOR pathway in regulating cellular processes during infection and indicate the involvement of EVs in intercellular communication. Additionally, the results identified potential biomarkers capable of aiding early diagnosis and assessing disease progression. <b>Conclusions:</b> This study demonstrates that EVs play a crucial role in intercellular communication during Zika virus infection. The identification of specific alterations in the PI3K-AKT-mTOR pathway highlights a possible therapeutic target, providing new opportunities for the development of more effective treatment strategies for CZS. Our findings significantly advance the understanding of CZS and underscore the need for further investigations using advanced techniques to validate and explore these potential molecular targets.https://www.mdpi.com/2218-273X/15/1/32Zika infectionextracellularvesiclesproteomemetabolome
spellingShingle Leticia Gomes-de-Pontes
Lucila Akune Barreiros
Lillian Nunes Gomes
Ranieri Coelho Salgado
Sarah Maria da Silva Napoleão
Paulo V. Soeiro-Pereira
Saulo Duarte Passos
Antonio Condino-Neto
Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis
Biomolecules
Zika infection
extracellular
vesicles
proteome
metabolome
title Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis
title_full Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis
title_fullStr Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis
title_full_unstemmed Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis
title_short Congenital Zika Syndrome: Insights from Integrated Proteomic and Metabolomic Analysis
title_sort congenital zika syndrome insights from integrated proteomic and metabolomic analysis
topic Zika infection
extracellular
vesicles
proteome
metabolome
url https://www.mdpi.com/2218-273X/15/1/32
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AT raniericoelhosalgado congenitalzikasyndromeinsightsfromintegratedproteomicandmetabolomicanalysis
AT sarahmariadasilvanapoleao congenitalzikasyndromeinsightsfromintegratedproteomicandmetabolomicanalysis
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