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Measles virus P protein suppresses Toll‐like receptor signal through up‐regulation of ubiquitin‐modifying enzyme A20
Author(s) -
Yokota Shinichi,
Okabayashi Tamaki,
Yokosawa Noriko,
Fujii Nobuhiro
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8976com
Subject(s) - measles virus , toll like receptor , biology , signal transduction , tlr4 , tumor necrosis factor alpha , protein kinase a , immune system , receptor , microbiology and biotechnology , kinase , virology , innate immune system , immunology , measles , vaccination , biochemistry
We recently reported that the activation of NF‐κB and AP‐1 was suppressed in monocytes infected with measles virus, but not in infected epithelial cells. This cell‐type‐specific suppression of the inflammatory re‐sponse represents a potential for measles virus to evade host immune system. In the current study, we examined the suppression mechanism of lipopolysaccharide (LPS)‐induced, namely Toll‐like receptor 4 (TLR4)‐mediated, activation of NF‐κB and AP‐1 in measles virus‐infected monocytic cells. In the infected cells, LPS treatment failed to induce the formation of active protein kinase complex containing TAK1, TAB2 and tumor necrosis factor receptor‐associated factor 6 (TRAF6), dissociate from TLR complexes containing Interleukin‐1 receptor‐associated kinase 1 (IRAK1). Ubiquitin‐modifying enzyme A20, which is a host negative feedback regulator of NF‐κB, was dramatically up‐regulated in infected monocytic cells, but not in infected epithelial cells. Suppression of A20 expression by siRNA restored LPS‐induced signaling in infected cells. Measles virus phosphoprotein (P protein) expression was necessary and sufficient for the induction of A20. P protein interacted indirectly with a negative regulatory motif in the A20 gene promoter, and released the suppression of A20 transcription, independent of the activation of NF‐κB.— Yokota, S., Okabayashi, T., Yokosawa, N., Fujii, N. Measles virus P protein suppresses Toll‐like receptor signal through up‐regulation of ubiquitin‐modi‐fying enzyme A20. FASEB J. 22, 74–83 (2008)