title: RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells.
abstract: 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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Bruno
authors.identifier: 0000-0002-4351-0102
authors.initials: B
authors.lastname: Hernáez
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Graciela
authors.initials: G
authors.lastname: Alonso
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Alonso-Lobo
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rastrojo
authors.affiliation: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092 Berlin, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13092 Berlin, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Sauer
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Aguado
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Antonio
authors.identifier: 0000-0002-3333-6016
authors.initials: A
authors.lastname: Alcamí
mesh_terms: D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002460:Cell Line; D005347:Fibroblasts / Q000276:immunology / Q000821:virology*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions / Q000235:genetics; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D014466:Ultraviolet Rays; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins; D014764:Viral Proteins; C067853:B18R protein, Vaccinia virus