Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome

In 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in infants who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZI...

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Main Authors: Janaina Macedo-da-Silva, Lívia Rosa-Fernandes, Raquel Hora Barbosa, Claudia B. Angeli, Fabiana Rabe Carvalho, Renata Artimos de Oliveira Vianna, Paulo C. Carvalho, Martin R. Larsen, Claudete Araújo Cardoso, Giuseppe Palmisano
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2020.577819/full
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author Janaina Macedo-da-Silva
Janaina Macedo-da-Silva
Lívia Rosa-Fernandes
Raquel Hora Barbosa
Claudia B. Angeli
Fabiana Rabe Carvalho
Fabiana Rabe Carvalho
Renata Artimos de Oliveira Vianna
Renata Artimos de Oliveira Vianna
Paulo C. Carvalho
Martin R. Larsen
Claudete Araújo Cardoso
Claudete Araújo Cardoso
Giuseppe Palmisano
author_facet Janaina Macedo-da-Silva
Janaina Macedo-da-Silva
Lívia Rosa-Fernandes
Raquel Hora Barbosa
Claudia B. Angeli
Fabiana Rabe Carvalho
Fabiana Rabe Carvalho
Renata Artimos de Oliveira Vianna
Renata Artimos de Oliveira Vianna
Paulo C. Carvalho
Martin R. Larsen
Claudete Araújo Cardoso
Claudete Araújo Cardoso
Giuseppe Palmisano
author_sort Janaina Macedo-da-Silva
collection DOAJ
description In 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in infants who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZIKV in the uterus have complications included in abnormalities related to Congenital Zika Syndrome (CZS). The risk of complications after birth is not well documented, however, clinical evidence shows that 6% of infants exposed to ZIKV during pregnancy have complications present at birth, and this rate rises to 14% when medical monitoring is performed in all exposed infants, regardless of birth condition. Thus, the evaluation and monitoring of all exposed infants are of foremost importance as the development of late complications has been increasingly supported by clinical evidence. The identification of changes in protein profile of infants exposed to ZIKV without CZS could provide valuable findings to better understand molecular changes in this cohort. Here, we use a shotgun-proteomics approach to investigate alterations in the serum of infants without CZS symptoms but exposed to intrauterine ZIKV (ZIKV) compared to unexposed controls (CTRL). A complex pattern of differentially expressed proteins was identified, highlighting the dysregulation of proteins involved in axon orientation, visual phototransduction, and global protease activity in children exposed to ZIKV without CZS. These data support the importance of monitoring children exposed to ZIKV during gestation and without early CZS symptoms. Our study is the first to assess molecular evidence of possible late disorders in children victims of the ZIKV outbreak in the Americas. We emphasize the importance of medical monitoring of symptomatic and asymptomatic children, as apparently unexplained late neurological and eye disorders may be due to intrauterine ZIKV exposure.
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spelling doaj.art-5e83556c97534b0894c867e50238918d2022-12-22T00:45:56ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-11-011010.3389/fcimb.2020.577819577819Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika SyndromeJanaina Macedo-da-Silva0Janaina Macedo-da-Silva1Lívia Rosa-Fernandes2Raquel Hora Barbosa3Claudia B. Angeli4Fabiana Rabe Carvalho5Fabiana Rabe Carvalho6Renata Artimos de Oliveira Vianna7Renata Artimos de Oliveira Vianna8Paulo C. Carvalho9Martin R. Larsen10Claudete Araújo Cardoso11Claudete Araújo Cardoso12Giuseppe Palmisano13GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, BrazilLaboratory for Structural and Computational Proteomics, Carlos Chagas Institute, Fiocruz, Curitiba, BrazilGlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, BrazilMaternal and Child Department, School of Medicine, Universidade Federal Fluminense, Niteroi, BrazilGlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, BrazilMaternal and Child Department, School of Medicine, Universidade Federal Fluminense, Niteroi, BrazilMultiuser Laboratory for Research in Nephrology and Medical Sciences (LAMAP), School of Medicine, Universidade Federal Fluminense, Niteroi, BrazilMaternal and Child Department, School of Medicine, Universidade Federal Fluminense, Niteroi, BrazilMultiuser Laboratory for Research in Nephrology and Medical Sciences (LAMAP), School of Medicine, Universidade Federal Fluminense, Niteroi, BrazilLaboratory for Structural and Computational Proteomics, Carlos Chagas Institute, Fiocruz, Curitiba, BrazilDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, DenmarkMaternal and Child Department, School of Medicine, Universidade Federal Fluminense, Niteroi, BrazilMultiuser Laboratory for Research in Nephrology and Medical Sciences (LAMAP), School of Medicine, Universidade Federal Fluminense, Niteroi, BrazilGlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, BrazilIn 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in infants who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZIKV in the uterus have complications included in abnormalities related to Congenital Zika Syndrome (CZS). The risk of complications after birth is not well documented, however, clinical evidence shows that 6% of infants exposed to ZIKV during pregnancy have complications present at birth, and this rate rises to 14% when medical monitoring is performed in all exposed infants, regardless of birth condition. Thus, the evaluation and monitoring of all exposed infants are of foremost importance as the development of late complications has been increasingly supported by clinical evidence. The identification of changes in protein profile of infants exposed to ZIKV without CZS could provide valuable findings to better understand molecular changes in this cohort. Here, we use a shotgun-proteomics approach to investigate alterations in the serum of infants without CZS symptoms but exposed to intrauterine ZIKV (ZIKV) compared to unexposed controls (CTRL). A complex pattern of differentially expressed proteins was identified, highlighting the dysregulation of proteins involved in axon orientation, visual phototransduction, and global protease activity in children exposed to ZIKV without CZS. These data support the importance of monitoring children exposed to ZIKV during gestation and without early CZS symptoms. Our study is the first to assess molecular evidence of possible late disorders in children victims of the ZIKV outbreak in the Americas. We emphasize the importance of medical monitoring of symptomatic and asymptomatic children, as apparently unexplained late neurological and eye disorders may be due to intrauterine ZIKV exposure.https://www.frontiersin.org/articles/10.3389/fcimb.2020.577819/fullZika viruslate abnormalitiesserum proteomicsmass spectrometrybiomarkerCongenital Zika Syndrome
spellingShingle Janaina Macedo-da-Silva
Janaina Macedo-da-Silva
Lívia Rosa-Fernandes
Raquel Hora Barbosa
Claudia B. Angeli
Fabiana Rabe Carvalho
Fabiana Rabe Carvalho
Renata Artimos de Oliveira Vianna
Renata Artimos de Oliveira Vianna
Paulo C. Carvalho
Martin R. Larsen
Claudete Araújo Cardoso
Claudete Araújo Cardoso
Giuseppe Palmisano
Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome
Frontiers in Cellular and Infection Microbiology
Zika virus
late abnormalities
serum proteomics
mass spectrometry
biomarker
Congenital Zika Syndrome
title Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome
title_full Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome
title_fullStr Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome
title_full_unstemmed Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome
title_short Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome
title_sort serum proteomics reveals alterations in protease activity axon guidance and visual phototransduction pathways in infants with in utero exposure to zika virus without congenital zika syndrome
topic Zika virus
late abnormalities
serum proteomics
mass spectrometry
biomarker
Congenital Zika Syndrome
url https://www.frontiersin.org/articles/10.3389/fcimb.2020.577819/full
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