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Measles virus P protein suppresses Toll-like receptor signal through up-regulation of ubiquitin-modifying enzyme A20

Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan

¹Correspondence: Department of Microbiology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo 060-8556, Japan. E-mail: fujii{at}sapmed.ac.jp

We recently reported that the activation of NF-B 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 response 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-B 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-B, 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-B.—Yokota, S., Okabayashi, T., Yokosawa, N., Fujii, N. Measles virus P protein suppresses Toll-like receptor signal through up-regulation of ubiquitin-modifying enzyme A20.

Key Words: viral infection • immunosuppression • TLR • monocyte • NF-B

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				M. Carsillo, K. Klapproth, and S. Niewiesk Cytokine Imbalance after Measles Virus Infection Has No Correlation with Immune Suppression J. Virol., July 15, 2009; 83(14): 7244 - 7251. [Abstract] [Full Text] [PDF]