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    A poxviral homolog of the Pellino protein inhibits Toll and Toll-like receptor signalling


    Griffin, Bryan D. and Mellett, Mark and Campos-Torres, Antonio and Kinsella, Gemma K. and Wang, Bingwei and Moynagh, Paul N. (2011) A poxviral homolog of the Pellino protein inhibits Toll and Toll-like receptor signalling. European Journal of Immunology, 41 (3). pp. 798-812.

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    Abstract

    Toll-like receptor (TLR) signalling pathways constitute an evolutionarily conserved component of the host immune response to pathogenic infection. Here, we describe the ability of a virally encoded form of the Pellino protein to inhibit Toll- and TLR-mediated activation of downstream Rel family transcription factors. In addition to inhibiting drosomycin promoter activation by Spa¨ tzle in Drosophila melanogaster cells, viral Pellino attenuates the activation of NF-jB by TLR signalling components and by the TLR4 ligand, LPS, in human cells. We propose that viral Pellino, like mammalian Pellinos, contains a forkhead-associated domain but differs from the mammalian forms in that it lacks a complete and functional RING-like domain. We produce a homology model and present experimental data to support this model by demonstrating that, like mammalian Pellinos, viral Pellino can interact with IRAK-1 via its forkhead-associated domain, whereas unlike its mammalian counterparts, it fails to post-translationally modify IRAK-1. Furthermore, we demonstrate that viral Pellino can functionally antagonise the activity of human Pellino3S. Thus, our findings identify potential immunoevasive capabilities possessed by a poxviral homolog of the Pellino protein and add growing evidence for a likely role for Pellino proteins in Toll and TLR signalling.

    Item Type: Article
    Additional Information: The definitive version of this article is available at DOI 10.1002/eji.201040774
    Keywords: Innate immunity; Pellino; Signal transduction; Toll-like receptors;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 4284
    Depositing User: Professor Paul Moynagh
    Date Deposited: 03 Apr 2013 16:09
    Journal or Publication Title: European Journal of Immunology
    Publisher: WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
    Refereed: Yes
    URI:

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