The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS
Zika virus (ZIKV) infection during pregnancy is associated with microcephaly, a congenital malformation resulting from neuroinflammation and direct effects of virus replication on the developing central nervous system (CNS). However, the exact changes in the affected CNS remain unknown. Here, we sho...
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-08-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01928/full |
id |
doaj-5143daf700724fa8940f9a326122bcf9 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Morganna C. Lima Leila R. de Mendonça Antonio M. Rezende Raquel M. Carrera Conceição E. Aníbal-Silva Matthew Demers Leonardo D'Aiuto Joel Wood Kodavali V. Chowdari Michael Griffiths Antonio R. Lucena-Araujo Manoel Barral-Netto Elisa A. N. Azevedo Renan W. Alves Pablo C. S. Farias Ernesto T. A. Marques Ernesto T. A. Marques Priscila M. S. Castanha Claire L. Donald Alain Kohl Vishwajit L. Nimgaonkar Vishwajit L. Nimgaonkar Rafael F. O. Franca |
spellingShingle |
Morganna C. Lima Leila R. de Mendonça Antonio M. Rezende Raquel M. Carrera Conceição E. Aníbal-Silva Matthew Demers Leonardo D'Aiuto Joel Wood Kodavali V. Chowdari Michael Griffiths Antonio R. Lucena-Araujo Manoel Barral-Netto Elisa A. N. Azevedo Renan W. Alves Pablo C. S. Farias Ernesto T. A. Marques Ernesto T. A. Marques Priscila M. S. Castanha Claire L. Donald Alain Kohl Vishwajit L. Nimgaonkar Vishwajit L. Nimgaonkar Rafael F. O. Franca The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS Frontiers in Immunology Zika virus central nervous system inflammation type-I interferon interferonopathy microcephaly |
author_facet |
Morganna C. Lima Leila R. de Mendonça Antonio M. Rezende Raquel M. Carrera Conceição E. Aníbal-Silva Matthew Demers Leonardo D'Aiuto Joel Wood Kodavali V. Chowdari Michael Griffiths Antonio R. Lucena-Araujo Manoel Barral-Netto Elisa A. N. Azevedo Renan W. Alves Pablo C. S. Farias Ernesto T. A. Marques Ernesto T. A. Marques Priscila M. S. Castanha Claire L. Donald Alain Kohl Vishwajit L. Nimgaonkar Vishwajit L. Nimgaonkar Rafael F. O. Franca |
author_sort |
Morganna C. Lima |
title |
The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS |
title_short |
The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS |
title_full |
The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS |
title_fullStr |
The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS |
title_full_unstemmed |
The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS |
title_sort |
transcriptional and protein profile from human infected neuroprogenitor cells is strongly correlated to zika virus microcephaly cytokines phenotype evidencing a persistent inflammation in the cns |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-08-01 |
description |
Zika virus (ZIKV) infection during pregnancy is associated with microcephaly, a congenital malformation resulting from neuroinflammation and direct effects of virus replication on the developing central nervous system (CNS). However, the exact changes in the affected CNS remain unknown. Here, we show by transcriptome analysis (at 48 h post-infection) and multiplex immune profiling that human induced-neuroprogenitor stem cells (hiNPCs) respond to ZIKV infection with a strong induction of type-I interferons (IFNs) and several type-I IFNs stimulated genes (ISGs), notably cytokines and the pro-apoptotic chemokines CXCL9 and CXCL10. By comparing the inflammatory profile induced by a ZIKV Brazilian strain with an ancestral strain isolated from Cambodia in 2010, we observed that the response magnitude differs among them. Compared to ZIKV/Cambodia, the experimental infection of hiNPCs with ZIKV/Brazil resulted in a diminished induction of ISGs and lower induction of several cytokines (IFN-α, IL-1α/β, IL-6, IL-8, and IL-15), consequently favoring virus replication. From ZIKV-confirmed infant microcephaly cases, we detected a similar profile characterized by the presence of IFN-α, CXCL10, and CXCL9 in cerebrospinal fluid (CSF) samples collected after birth, evidencing a sustained CNS inflammation. Altogether, our data suggest that the CNS may be directly affected due to an unbalanced and chronic local inflammatory response, elicited by ZIKV infection, which contributes to damage to the fetal brain. |
topic |
Zika virus central nervous system inflammation type-I interferon interferonopathy microcephaly |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.01928/full |
work_keys_str_mv |
AT morgannaclima thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT leilardemendonca thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT antoniomrezende thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT raquelmcarrera thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT conceicaoeanibalsilva thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT matthewdemers thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT leonardodaiuto thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT joelwood thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT kodavalivchowdari thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT michaelgriffiths thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT antoniorlucenaaraujo thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT manoelbarralnetto thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT elisaanazevedo thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT renanwalves thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT pablocsfarias thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT ernestotamarques thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT ernestotamarques thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT priscilamscastanha thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT claireldonald thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT alainkohl thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT vishwajitlnimgaonkar thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT vishwajitlnimgaonkar thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT rafaelfofranca thetranscriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT morgannaclima transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT leilardemendonca transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT antoniomrezende transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT raquelmcarrera transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT conceicaoeanibalsilva transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT matthewdemers transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT leonardodaiuto transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT joelwood transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT kodavalivchowdari transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT michaelgriffiths transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT antoniorlucenaaraujo transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT manoelbarralnetto transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT elisaanazevedo transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT renanwalves transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT pablocsfarias transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT ernestotamarques transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT ernestotamarques transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT priscilamscastanha transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT claireldonald transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT alainkohl transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT vishwajitlnimgaonkar transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT vishwajitlnimgaonkar transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns AT rafaelfofranca transcriptionalandproteinprofilefromhumaninfectedneuroprogenitorcellsisstronglycorrelatedtozikavirusmicrocephalycytokinesphenotypeevidencingapersistentinflammationinthecns |
_version_ |
1725081462556852224 |
spelling |
doaj-5143daf700724fa8940f9a326122bcf92020-11-25T01:32:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-08-011010.3389/fimmu.2019.01928474153The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNSMorganna C. Lima0Leila R. de Mendonça1Antonio M. Rezende2Raquel M. Carrera3Conceição E. Aníbal-Silva4Matthew Demers5Leonardo D'Aiuto6Joel Wood7Kodavali V. Chowdari8Michael Griffiths9Antonio R. Lucena-Araujo10Manoel Barral-Netto11Elisa A. N. Azevedo12Renan W. Alves13Pablo C. S. Farias14Ernesto T. A. Marques15Ernesto T. A. Marques16Priscila M. S. Castanha17Claire L. Donald18Alain Kohl19Vishwajit L. Nimgaonkar20Vishwajit L. Nimgaonkar21Rafael F. O. Franca22Oswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilInstitute of Infection and Global Health, University of Liverpool, Liverpool, United KingdomOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesInstitute of Infection and Global Health, University of Liverpool, Liverpool, United KingdomFederal University of Pernambuco/UFPE, Recife, BrazilOswaldo Cruz Foundation/Fiocruz, Institute Gonçalo Moniz, Salvador, BrazilOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilCenter for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United StatesMRC-University of Glasgow Centre for Virus Research, Glasgow, United KingdomMRC-University of Glasgow Centre for Virus Research, Glasgow, United KingdomDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesOswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, BrazilZika virus (ZIKV) infection during pregnancy is associated with microcephaly, a congenital malformation resulting from neuroinflammation and direct effects of virus replication on the developing central nervous system (CNS). However, the exact changes in the affected CNS remain unknown. Here, we show by transcriptome analysis (at 48 h post-infection) and multiplex immune profiling that human induced-neuroprogenitor stem cells (hiNPCs) respond to ZIKV infection with a strong induction of type-I interferons (IFNs) and several type-I IFNs stimulated genes (ISGs), notably cytokines and the pro-apoptotic chemokines CXCL9 and CXCL10. By comparing the inflammatory profile induced by a ZIKV Brazilian strain with an ancestral strain isolated from Cambodia in 2010, we observed that the response magnitude differs among them. Compared to ZIKV/Cambodia, the experimental infection of hiNPCs with ZIKV/Brazil resulted in a diminished induction of ISGs and lower induction of several cytokines (IFN-α, IL-1α/β, IL-6, IL-8, and IL-15), consequently favoring virus replication. From ZIKV-confirmed infant microcephaly cases, we detected a similar profile characterized by the presence of IFN-α, CXCL10, and CXCL9 in cerebrospinal fluid (CSF) samples collected after birth, evidencing a sustained CNS inflammation. Altogether, our data suggest that the CNS may be directly affected due to an unbalanced and chronic local inflammatory response, elicited by ZIKV infection, which contributes to damage to the fetal brain.https://www.frontiersin.org/article/10.3389/fimmu.2019.01928/fullZika viruscentral nervous systeminflammationtype-I interferoninterferonopathymicrocephaly |