[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
Front Immunol. 2019 Aug 16;10:1928. doi: 10.3389/fimmu.2019.01928. eCollection 2019.
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 MC1, de Mendonça LR1, Rezende AM1, Carrera RM2, Aníbal-Silva CE1, Demers M3, D’Aiuto L3, Wood J3, Chowdari KV3, Griffiths M2, Lucena-Araujo AR4, Barral-Netto M5, Azevedo EAN1, Alves RW1, Farias PCS1, Marques ETA1,6, Castanha PMS6, Donald CL7, Kohl A7, Nimgaonkar VL3,8, Franca RFO1.
Author information: 1 Oswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, Brazil. 2 Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. 3 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 4 Federal University of Pernambuco/UFPE, Recife, Brazil. 5 Oswaldo Cruz Foundation/Fiocruz, Institute Gonçalo Moniz, Salvador, Brazil. 6 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United States. 7 MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom. 8 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.
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: Zika congenital syndrome and cytokines; Zika virus; central nervous system; inflammation; interferonopathy; microcephaly; type-I interferon
PMID: 31474994 PMCID: PMC6707094 DOI: 10.3389/fimmu.2019.01928
Keywords: Zika Virus; Microcephaly; Zika Congenital Syndrome.