Author | Lima, Morganna C. | |
Author | Mendonça, Leila R. de | |
Author | Rezende, Antonio M. | |
Author | Carrera, Raquel M. | |
Author | Silva, Conceição Elidianne Anibal | |
Author | Demers, Matthew | |
Author | D'Aiuto, Leonardo | |
Author | Wood, Joel | |
Author | Chowdari, Kodavali V. | |
Author | Griffiths, Michael | |
Author | Araujo, Antonio R. Lucena | |
Author | Barral Netto, Manoel | |
Author | Azevedo, Elisa A. N. | |
Author | Alves, Renan W. | |
Author | Farias, Pablo C. S. | |
Author | Marques, Ernesto T. A. | |
Author | Castanha, Priscila M. S. | |
Author | Donald, Claire L. | |
Author | Kohl, Alain | |
Author | Nimgaonkar, Vishwajit L. | |
Author | Franca, Rafael F. O. | |
Access date | 2019-09-27T17:57:48Z | |
Available date | 2019-09-27T17:57:48Z | |
Document date | 2019 | |
Citation | LIMA, Morganna C. et al. 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, v. 10, p. 1-14, Aug. 2019. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/35979 | |
Sponsorship | Fundação de Amparo à Ciência e Tecnologia de Pernambuco/FACEPE, grant agreement nos. APQ-0055.2.11/16 and APQ-0044.2.11/16, and Conselho Nacional de Desenvolvimento Científico e Tecnológico/CNPq
grant agreement 439975/2016-6 under RF coordination and responsibility. UK Medical Research Council Grants MC_UU_12014/8 and MR/N017552/1 under AK’s coordination. VN received grant support from the Stanley Medical Research Institute (07R-1712), National Institutes of Health (MH63480 and D43 TW009114) and Cura Zika—University of Pittsburgh. | pt_BR |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Vírus zika | pt_BR |
Subject in Portuguese | Sistema nervoso central | pt_BR |
Subject in Portuguese | Inflamação | pt_BR |
Subject in Portuguese | Interferon tipo I | pt_BR |
Subject in Portuguese | Interferonopatia | pt_BR |
Subject in Portuguese | Microcefalia | pt_BR |
Subject in Portuguese | Síndrome congênita do zika e citocinas | pt_BR |
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 | pt_BR |
Type | Article | pt_BR |
DOI | 10.3389/fimmu.2019.01928 | |
Abstract | 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. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Affilliation | University of Liverpool. Institute of Infection and Global Health. Liverpool, United Kingdom. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Affilliation | University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States. | pt_BR |
Affilliation | University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States. | pt_BR |
Affilliation | University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States. | pt_BR |
Affilliation | University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States. | pt_BR |
Affilliation | University of Liverpool. Institute of Infection and Global Health. Liverpool, United Kingdom. | pt_BR |
Affilliation | Federal University of Pernambuco. Recife, PE, Brazil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil / University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, United States. | pt_BR |
Affilliation | University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, United States. | pt_BR |
Affilliation | University of Glasgow Centre for Virus Research. Glasgow, United Kingdom. | pt_BR |
Affilliation | University of Glasgow Centre for Virus Research. Glasgow, United Kingdom. | pt_BR |
Affilliation | University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States / University of Pittsburgh. Graduate School of Public Health. Department of Human Genetics. Pittsburgh, PA, United States. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
Subject | Zika virus | pt_BR |
Subject | Central nervous system | pt_BR |
Subject | Inflammation | pt_BR |
Subject | Type-I interferon | pt_BR |
Subject | Interferonopathy | pt_BR |
Subject | Microcephaly | pt_BR |
Subject | Zika congenital syndrome and cytokines | pt_BR |