RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells

Vaccinia virus (VACV) encodes the soluble type I interferon (IFN) binding protein B18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host IFN response. By using next generation sequencing technologies, we performed a detaile...

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Main Authors: Bruno Hernáez, Graciela Alonso, Juan Manuel Alonso-Lobo, Alberto Rastrojo, Cornelius Fischer, Sascha Sauer, Begoña Aguado, Antonio Alcamí
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2017/5157626
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author Bruno Hernáez
Graciela Alonso
Juan Manuel Alonso-Lobo
Alberto Rastrojo
Cornelius Fischer
Sascha Sauer
Begoña Aguado
Antonio Alcamí
author_facet Bruno Hernáez
Graciela Alonso
Juan Manuel Alonso-Lobo
Alberto Rastrojo
Cornelius Fischer
Sascha Sauer
Begoña Aguado
Antonio Alcamí
author_sort Bruno Hernáez
collection DOAJ
description Vaccinia virus (VACV) encodes the soluble type I interferon (IFN) binding protein B18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host IFN response. By using next generation sequencing technologies, we performed a detailed RNA-seq study to dissect at the transcriptional level the modulation of the IFN based host response by VACV and B18. Transcriptome profiling of L929 cells after incubation with purified recombinant B18 protein showed that attachment of B18 to the cell surface does not trigger cell signalling leading to transcriptional activation. Consistent with its ability to bind type I IFN, B18 completely inhibited the IFN-mediated modulation of host gene expression. Addition of UV-inactivated virus particles to cell cultures altered the expression of a set of 53 cellular genes, including genes involved in innate immunity. Differential gene expression analyses of cells infected with replication competent VACV identified the activation of a broad range of host genes involved in multiple cellular pathways. Interestingly, we did not detect an IFN-mediated response among the transcriptional changes induced by VACV, even after the addition of IFN to cells infected with a mutant VACV lacking B18. This is consistent with additional viral mechanisms acting at different levels to block IFN responses during VACV infection.
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spelling doaj-art-49b4319b679e45f6abfaf4ee658d60c92025-02-03T05:44:24ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/51576265157626RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse CellsBruno Hernáez0Graciela Alonso1Juan Manuel Alonso-Lobo2Alberto Rastrojo3Cornelius Fischer4Sascha Sauer5Begoña Aguado6Antonio Alcamí7Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, SpainCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, SpainCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, SpainCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, SpainMax Planck Institute for Molecular Genetics, 14195 Berlin, GermanyMax Planck Institute for Molecular Genetics, 14195 Berlin, GermanyCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, SpainCentro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, SpainVaccinia virus (VACV) encodes the soluble type I interferon (IFN) binding protein B18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host IFN response. By using next generation sequencing technologies, we performed a detailed RNA-seq study to dissect at the transcriptional level the modulation of the IFN based host response by VACV and B18. Transcriptome profiling of L929 cells after incubation with purified recombinant B18 protein showed that attachment of B18 to the cell surface does not trigger cell signalling leading to transcriptional activation. Consistent with its ability to bind type I IFN, B18 completely inhibited the IFN-mediated modulation of host gene expression. Addition of UV-inactivated virus particles to cell cultures altered the expression of a set of 53 cellular genes, including genes involved in innate immunity. Differential gene expression analyses of cells infected with replication competent VACV identified the activation of a broad range of host genes involved in multiple cellular pathways. Interestingly, we did not detect an IFN-mediated response among the transcriptional changes induced by VACV, even after the addition of IFN to cells infected with a mutant VACV lacking B18. This is consistent with additional viral mechanisms acting at different levels to block IFN responses during VACV infection.http://dx.doi.org/10.1155/2017/5157626
spellingShingle Bruno Hernáez
Graciela Alonso
Juan Manuel Alonso-Lobo
Alberto Rastrojo
Cornelius Fischer
Sascha Sauer
Begoña Aguado
Antonio Alcamí
RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells
Journal of Immunology Research
title RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells
title_full RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells
title_fullStr RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells
title_full_unstemmed RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells
title_short RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells
title_sort rna seq based transcriptome analysis of the type i interferon host response upon vaccinia virus infection of mouse cells
url http://dx.doi.org/10.1155/2017/5157626
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