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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
Lima, Morganna C. et al. | Date Issued: 2019
Author
Lima, Morganna C.
Mendonça, Leila R. de
Rezende, Antonio M.
Carrera, Raquel M.
Silva, Conceição Elidianne Anibal
Demers, Matthew
D'Aiuto, Leonardo
Wood, Joel
Chowdari, Kodavali V.
Griffiths, Michael
Araujo, Antonio R. Lucena
Barral Netto, Manoel
Azevedo, Elisa A. N.
Alves, Renan W.
Farias, Pablo C. S.
Marques, Ernesto T. A.
Castanha, Priscila M. S.
Donald, Claire L.
Kohl, Alain
Nimgaonkar, Vishwajit L.
Franca, Rafael F. O.
Affilliation
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
University of Liverpool. Institute of Infection and Global Health. Liverpool, United Kingdom.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States.
University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States.
University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States.
University of Pittsburgh. School of Medicine. Department of Psychiatry. Pittsburgh, PA, United States.
University of Liverpool. Institute of Infection and Global Health. Liverpool, United Kingdom.
Federal University of Pernambuco. Recife, PE, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil / University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, United States.
University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, United States.
University of Glasgow Centre for Virus Research. Glasgow, United Kingdom.
University of Glasgow Centre for Virus Research. Glasgow, United Kingdom.
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.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
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.
Keywords in Portuguese
Vírus zika
Sistema nervoso central
Inflamação
Interferon tipo I
Interferonopatia
Microcefalia
Síndrome congênita do zika e citocinas
 
Keywords
Zika virus
Central nervous system
Inflammation
Type-I interferon
Interferonopathy
Microcephaly
Zika congenital syndrome and cytokines
 
Publisher
Frontiers Media
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.
DOI
10.3389/fimmu.2019.01928
ISSN
1664-3224