microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection
Viral infections have always been a serious burden to public health, increasing morbidity and mortality rates worldwide. Zika virus (ZIKV) is a flavivirus transmitted by the <i>Aedes aegypti</i> vector and the causative agent of severe fetal neuropathogenesis and microcephaly. The virus...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10282 |
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| author | Carolina M. Polonio Patrick da Silva Fabiele B. Russo Brendo R. N. Hyppolito Nagela G. Zanluqui Cecília Benazzato Patrícia C. B. Beltrão-Braga Sandra M. Muxel Jean Pierre S. Peron |
| author_facet | Carolina M. Polonio Patrick da Silva Fabiele B. Russo Brendo R. N. Hyppolito Nagela G. Zanluqui Cecília Benazzato Patrícia C. B. Beltrão-Braga Sandra M. Muxel Jean Pierre S. Peron |
| author_sort | Carolina M. Polonio |
| collection | DOAJ |
| description | Viral infections have always been a serious burden to public health, increasing morbidity and mortality rates worldwide. Zika virus (ZIKV) is a flavivirus transmitted by the <i>Aedes aegypti</i> vector and the causative agent of severe fetal neuropathogenesis and microcephaly. The virus crosses the placenta and reaches the fetal brain, mainly causing the death of neuronal precursor cells (NPCs), glial inflammation, and subsequent tissue damage. Genetic differences, mainly related to the antiviral immune response and cell death pathways greatly influence the susceptibility to infection. These components are modulated by many factors, including microRNAs (miRNAs). MiRNAs are small noncoding RNAs that regulate post-transcriptionally the overall gene expression, including genes for the neurodevelopment and the formation of neural circuits. In this context, we investigated the pathways and target genes of miRNAs modulated in NPCs infected with ZIKV. We observed downregulation of miR-302b, miR-302c and miR-194, whereas miR-30c was upregulated in ZIKV infected human NPCs in vitro. The analysis of a public dataset of ZIKV-infected human NPCs evidenced 262 upregulated and 3 downregulated genes, of which 142 were the target of the aforementioned miRNAs. Further, we confirmed a correlation between miRNA and target genes affecting pathways related to antiviral immune response, cell death and immune cells chemotaxis, all of which could contribute to the establishment of microcephaly and brain lesions. Here, we suggest that miRNAs target gene expression in infected NPCs, directly contributing to the pathogenesis of fetal microcephaly. |
| first_indexed | 2024-03-09T23:48:34Z |
| format | Article |
| id | doaj.art-438796f597d8469f8168c7e0609e1172 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:48:34Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-438796f597d8469f8168c7e0609e11722023-11-23T16:39:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181028210.3390/ijms231810282microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus InfectionCarolina M. Polonio0Patrick da Silva1Fabiele B. Russo2Brendo R. N. Hyppolito3Nagela G. Zanluqui4Cecília Benazzato5Patrícia C. B. Beltrão-Braga6Sandra M. Muxel7Jean Pierre S. Peron8Neuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo 05508-000, BrazilNeuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo 05508-000, BrazilScientific Platform Pasteur-USP (SPPU), University of São Paulo, São Paulo 05508-000, BrazilNeuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo 05508-000, BrazilNeuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo 05508-000, BrazilDisease Modeling Laboratory at Department of Microbiology, Institute of Biomedical Sciences, São Paulo 05508-000, BrazilScientific Platform Pasteur-USP (SPPU), University of São Paulo, São Paulo 05508-000, BrazilNeuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo 05508-000, BrazilNeuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo 05508-000, BrazilViral infections have always been a serious burden to public health, increasing morbidity and mortality rates worldwide. Zika virus (ZIKV) is a flavivirus transmitted by the <i>Aedes aegypti</i> vector and the causative agent of severe fetal neuropathogenesis and microcephaly. The virus crosses the placenta and reaches the fetal brain, mainly causing the death of neuronal precursor cells (NPCs), glial inflammation, and subsequent tissue damage. Genetic differences, mainly related to the antiviral immune response and cell death pathways greatly influence the susceptibility to infection. These components are modulated by many factors, including microRNAs (miRNAs). MiRNAs are small noncoding RNAs that regulate post-transcriptionally the overall gene expression, including genes for the neurodevelopment and the formation of neural circuits. In this context, we investigated the pathways and target genes of miRNAs modulated in NPCs infected with ZIKV. We observed downregulation of miR-302b, miR-302c and miR-194, whereas miR-30c was upregulated in ZIKV infected human NPCs in vitro. The analysis of a public dataset of ZIKV-infected human NPCs evidenced 262 upregulated and 3 downregulated genes, of which 142 were the target of the aforementioned miRNAs. Further, we confirmed a correlation between miRNA and target genes affecting pathways related to antiviral immune response, cell death and immune cells chemotaxis, all of which could contribute to the establishment of microcephaly and brain lesions. Here, we suggest that miRNAs target gene expression in infected NPCs, directly contributing to the pathogenesis of fetal microcephaly.https://www.mdpi.com/1422-0067/23/18/10282microRNAZIKVinflammationcell deathchemotaxis |
| spellingShingle | Carolina M. Polonio Patrick da Silva Fabiele B. Russo Brendo R. N. Hyppolito Nagela G. Zanluqui Cecília Benazzato Patrícia C. B. Beltrão-Braga Sandra M. Muxel Jean Pierre S. Peron microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection International Journal of Molecular Sciences microRNA ZIKV inflammation cell death chemotaxis |
| title | microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection |
| title_full | microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection |
| title_fullStr | microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection |
| title_full_unstemmed | microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection |
| title_short | microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection |
| title_sort | micrornas control antiviral immune response cell death and chemotaxis pathways in human neuronal precursor cells npcs during zika virus infection |
| topic | microRNA ZIKV inflammation cell death chemotaxis |
| url | https://www.mdpi.com/1422-0067/23/18/10282 |
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