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RNA-seq based transcriptome analysis of the type I interferon host response upon vaccinia virus infection of mouse cells

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Item Type:Article
Title:RNA-seq based transcriptome analysis of the type I interferon host response upon vaccinia virus infection of mouse cells
Creators Name:Hernáez, B. and Alonso, G. and Alonso-Lobo, J.M. and Rastrojo, A. and Fischer, C. and Sauer, S. and Aguado, B. and Alcamí, A.
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.
Keywords:Base Sequence, Cell Line, Fibroblasts, Gene Expression, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Host-Pathogen Interactions, Interferon Type I, Mutation, Real-Time Polymerase Chain Reaction, Recombinant Proteins, Ultraviolet Rays, Vaccinia virus, Viral Proteins, Virus Replication, Animals, Mice
Source:Journal of Immunology Research
Page Range:5157626
Date:9 February 2017
Official Publication:https://doi.org/10.1155/2017/5157626
PubMed:View item in PubMed

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