In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays
The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/los...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/2/270 |
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| author | Rossella Gratton Paola Maura Tricarico Almerinda Agrelli Heverton Valentim Colaço da Silva Lucas Coêlho Bernardo Sergio Crovella Antonio Victor Campos Coelho Ronald Rodrigues de Moura Lucas André Cavalcanti Brandão |
| author_facet | Rossella Gratton Paola Maura Tricarico Almerinda Agrelli Heverton Valentim Colaço da Silva Lucas Coêlho Bernardo Sergio Crovella Antonio Victor Campos Coelho Ronald Rodrigues de Moura Lucas André Cavalcanti Brandão |
| author_sort | Rossella Gratton |
| collection | DOAJ |
| description | The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite recent advances, little is known about the pathways involved in CZS pathogenesis. We performed a meta-analysis, gene ontology (GO), and pathway analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during hNPCs infection with ZIKV. We selected three studies (17 samples of infected hPNCs compared to hPNCs uninfected controls) through a systematic search of the Gene Expression Omnibus (GEO) database. The raw reads were trimmed, counted, and normalized. Next, we performed a rank product meta-analysis to detect consistently differentially expressed genes (DEGs) in these independent experiments. We detected 13 statistically significant DEGs. GO ontology and reactome analysis showed an enrichment of interferon, pro-inflammatory, and chemokines signaling and apoptosis pathways in ZIKV-infected cells. Moreover, we detected three possible new candidate genes involved in hNPCs infection: <i>APOL6</i>, <i>XAF1</i>, and <i>TNFRSF1</i>. Our results confirm that interferon (IFN) signaling dominates the ZIKV response, and that a crucial contribution is given by apoptotic pathways, which might elicit the CZS phenotype. |
| first_indexed | 2024-04-13T18:55:30Z |
| format | Article |
| id | doaj.art-76001435332141bdaf4fc48f3a60c56f |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-04-13T18:55:30Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-76001435332141bdaf4fc48f3a60c56f2022-12-22T02:34:17ZengMDPI AGMicroorganisms2076-26072020-02-018227010.3390/microorganisms8020270microorganisms8020270In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq AssaysRossella Gratton0Paola Maura Tricarico1Almerinda Agrelli2Heverton Valentim Colaço da Silva3Lucas Coêlho Bernardo4Sergio Crovella5Antonio Victor Campos Coelho6Ronald Rodrigues de Moura7Lucas André Cavalcanti Brandão8Department of Advanced Translational Microbiology, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137 Trieste, ItalyDepartment of Advanced Translational Microbiology, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137 Trieste, ItalyLaboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235 Cidade Universitária, 50670-901 Recife, BrazilLaboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235 Cidade Universitária, 50670-901 Recife, BrazilLaboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235 Cidade Universitária, 50670-901 Recife, BrazilDepartment of Advanced Translational Microbiology, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137 Trieste, ItalyDepartment of Molecular Biology-Federal University of Paraíba (UFPB), Campus I-Lot.-Cidade Universitária, 58051-900 João Pessoa, BrazilDepartment of Pathology-Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235-Cidade Universitária, 50670-901 Recife, BrazilLaboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235 Cidade Universitária, 50670-901 Recife, BrazilThe Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite recent advances, little is known about the pathways involved in CZS pathogenesis. We performed a meta-analysis, gene ontology (GO), and pathway analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during hNPCs infection with ZIKV. We selected three studies (17 samples of infected hPNCs compared to hPNCs uninfected controls) through a systematic search of the Gene Expression Omnibus (GEO) database. The raw reads were trimmed, counted, and normalized. Next, we performed a rank product meta-analysis to detect consistently differentially expressed genes (DEGs) in these independent experiments. We detected 13 statistically significant DEGs. GO ontology and reactome analysis showed an enrichment of interferon, pro-inflammatory, and chemokines signaling and apoptosis pathways in ZIKV-infected cells. Moreover, we detected three possible new candidate genes involved in hNPCs infection: <i>APOL6</i>, <i>XAF1</i>, and <i>TNFRSF1</i>. Our results confirm that interferon (IFN) signaling dominates the ZIKV response, and that a crucial contribution is given by apoptotic pathways, which might elicit the CZS phenotype.https://www.mdpi.com/2076-2607/8/2/270congenital zika syndrometranscriptomicsgenomicsapoptosisgene ontologypathway analysisstem cells |
| spellingShingle | Rossella Gratton Paola Maura Tricarico Almerinda Agrelli Heverton Valentim Colaço da Silva Lucas Coêlho Bernardo Sergio Crovella Antonio Victor Campos Coelho Ronald Rodrigues de Moura Lucas André Cavalcanti Brandão In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays Microorganisms congenital zika syndrome transcriptomics genomics apoptosis gene ontology pathway analysis stem cells |
| title | In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays |
| title_full | In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays |
| title_fullStr | In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays |
| title_full_unstemmed | In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays |
| title_short | In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays |
| title_sort | in vitro zika virus infection of human neural progenitor cells meta analysis of rna seq assays |
| topic | congenital zika syndrome transcriptomics genomics apoptosis gene ontology pathway analysis stem cells |
| url | https://www.mdpi.com/2076-2607/8/2/270 |
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