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A poxviral homolog of the Pellino protein inhibits Toll and Toll-like receptor signalling
European Journal of Immunology (2011)
  • Byran D Griffin, Dr, National University of Ireland, Maynooth
  • Mark Mellett, Dr
  • Gemma K Kinsella, Dr, National University of Ireland, Maynooth
  • Antonio Campos-Torres, Dr, National University of Ireland, Maynooth
  • Bingwei Wang, Dr, National University of Ireland, Maynooth
  • Paul N Moynagh, Prof, National University of Ireland, Maynooth
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 Spätzle in Drosophila melanogaster cells, viral Pellino attenuates the activation of NF-κB 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.

Keywords
  • Innate immunity,
  • Pellino,
  • Signal transduction,
  • Toll-like receptors
Disciplines
Publication Date
Spring February 2, 2011
Citation Information
Byran D Griffin, Mark Mellett, Gemma K Kinsella, Antonio Campos-Torres, et al.. "A poxviral homolog of the Pellino protein inhibits Toll and Toll-like receptor signalling" European Journal of Immunology Vol. 41 Iss. 3 (2011)
Available at: http://works.bepress.com/gemma_kinsella/8/