Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors
Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022002070 |
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| author | Martin Selinger Pavlína Věchtová Hana Tykalová Petra Ošlejšková Michaela Rumlová Ján Štěrba Libor Grubhoffer |
| author_facet | Martin Selinger Pavlína Věchtová Hana Tykalová Petra Ošlejšková Michaela Rumlová Ján Štěrba Libor Grubhoffer |
| author_sort | Martin Selinger |
| collection | DOAJ |
| description | Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in vitro in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Infection with severe but not mild TBEV strain resulted in a high neuronal death rate. In comparison, infection with either of TBEV strains in human astrocytes did not. Differential expression and splicing analyses with an in silico prediction of miRNA/mRNA/lncRNA/vd-sRNA networks found significant changes in inflammatory and immune response pathways, nervous system development and regulation of mitosis in TBEV Hypr-infected neurons. Candidate mechanisms responsible for the aforementioned phenomena include specific regulation of host mRNA levels via differentially expressed miRNAs/lncRNAs or vd-sRNAs mimicking endogenous miRNAs and virus-driven modulation of host pre-mRNA splicing. We suggest that these factors are responsible for the observed differences in the virulence manifestation of both TBEV strains in different cell lines. This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis. |
| first_indexed | 2024-04-11T05:19:37Z |
| format | Article |
| id | doaj.art-86a306273e9145be900383d97905308f |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:37Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-86a306273e9145be900383d97905308f2022-12-24T04:52:45ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012027592777Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectorsMartin Selinger0Pavlína Věchtová1Hana Tykalová2Petra Ošlejšková3Michaela Rumlová4Ján Štěrba5Libor Grubhoffer6Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech Republic; Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, České Budějovice 370 05, Czech Republic; Corresponding author at: Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech Republic.Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech RepublicFaculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech Republic; Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, České Budějovice 370 05, Czech RepublicFaculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech RepublicDepartment of Biotechnology, University of Chemistry and Technology, Prague 166 28, Czech RepublicFaculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech RepublicFaculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech Republic; Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská 31, České Budějovice 370 05, Czech RepublicTick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in vitro in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Infection with severe but not mild TBEV strain resulted in a high neuronal death rate. In comparison, infection with either of TBEV strains in human astrocytes did not. Differential expression and splicing analyses with an in silico prediction of miRNA/mRNA/lncRNA/vd-sRNA networks found significant changes in inflammatory and immune response pathways, nervous system development and regulation of mitosis in TBEV Hypr-infected neurons. Candidate mechanisms responsible for the aforementioned phenomena include specific regulation of host mRNA levels via differentially expressed miRNAs/lncRNAs or vd-sRNAs mimicking endogenous miRNAs and virus-driven modulation of host pre-mRNA splicing. We suggest that these factors are responsible for the observed differences in the virulence manifestation of both TBEV strains in different cell lines. This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis.http://www.sciencedirect.com/science/article/pii/S2001037022002070Alternative splicingAstrocytesmiRNANeuronsResponse to infectionNeuropathogenesis |
| spellingShingle | Martin Selinger Pavlína Věchtová Hana Tykalová Petra Ošlejšková Michaela Rumlová Ján Štěrba Libor Grubhoffer Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors Computational and Structural Biotechnology Journal Alternative splicing Astrocytes miRNA Neurons Response to infection Neuropathogenesis |
| title | Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors |
| title_full | Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors |
| title_fullStr | Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors |
| title_full_unstemmed | Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors |
| title_short | Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors |
| title_sort | integrative rna profiling of tbev infected neurons and astrocytes reveals potential pathogenic effectors |
| topic | Alternative splicing Astrocytes miRNA Neurons Response to infection Neuropathogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022002070 |
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