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Disruption of Akt kinase activation is important for immunosuppression induced by measles virus

Nature Medicine volume 7, pages 725–731 (2001)Cite this article

Abstract

Surface-contact–mediated signaling induced by the measles virus (MV) fusion and hemagglutinin glycoproteins is necessary and sufficient to induce T-cell unresponsiveness in vitro and in vivo. To define the intracellular pathways involved, we analyzed interleukin (IL)-2R signaling in primary human T cells and in Kit-225 cells. Unlike IL-2–dependent activation of JAK/STAT pathways, activation of Akt kinase was impaired after MV contact both in vitro and in vivo. MV interference with Akt activation was important for immunosuppression, as expression of a catalytically active Akt prevented negative signaling by the MV glycoproteins. Thus, we show here that MV exploits a novel strategy to interfere with T-cell activation during immunosuppression.

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Figure 1: UV-MV abolish IL-2–stimulated proliferation of human PBL and Kit-225 cells.
Figure 2: IL-2–stimulated activation of JAK/STAT pathways in UV-MV–treated PBT cells.
Figure 3: UV-MV inhibits IL-2–dependent Akt activation in T cells.
Figure 4: UV-MV disrupts IL-2–dependent Akt-signaling but not BAD phosphorylation.
Figure 5: Expression of myr-Akt efficiently reduces MV-induced immunosuppression in vitro.

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Acknowledgements

We thank J. Schneider-Schaulies, A. Weidmann, I. Klagge and E. Serfling for helpful discussions; R. Grassmann for providing C91PL, JuanaW and HTLV-I Tax-transformed TAXI-1 cells; D. Cantrell for providing Kit-225 cells; and C. Rüth for technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft and the Bundesministerium Bildung and Forschung.

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Authors and Affiliations

  1. Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany

    Elita Avota, Stefan Niewiesk, Ursula Bommhardt, Volker ter Meulen & Sibylle Schneider-Schaulies

  2. Institute for Medical Radiation and Cell Research, University of Würzburg, Würzburg, Germany

    Andris Avots

  3. Department of Medicine, University of California, San Francisco, California, USA

    Lawrence P. Kane

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Correspondence to Sibylle Schneider-Schaulies.

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Avota, E., Avots, A., Niewiesk, S. et al. Disruption of Akt kinase activation is important for immunosuppression induced by measles virus. Nat Med 7, 725–731 (2001). https://doi.org/10.1038/89106

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