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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / pharmacology
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Animals
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Apoptosis / drug effects
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Carrier Proteins / metabolism
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Cell Line
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Chromones / pharmacology
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Hemagglutinins, Viral / metabolism
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Humans
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Immune Tolerance*
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Interleukin-2 / metabolism
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Janus Kinase 1
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Janus Kinase 3
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Lymphocyte Activation
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Measles / immunology*
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Measles / virology
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Measles virus / immunology*
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Measles virus / metabolism
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Measles virus / radiation effects
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Mice
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Mice, Transgenic
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Milk Proteins*
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Morpholines / pharmacology
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Protein Serine-Threonine Kinases*
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / immunology
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Receptors, Interleukin-2 / metabolism*
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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Sigmodontinae
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Signal Transduction / physiology*
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Spleen / cytology
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Trans-Activators / metabolism
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Viral Fusion Proteins / metabolism
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Wortmannin
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bcl-Associated Death Protein
Substances
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Androstadienes
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BAD protein, human
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Bad protein, mouse
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Carrier Proteins
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Chromones
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DNA-Binding Proteins
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Enzyme Inhibitors
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Hemagglutinins, Viral
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Interleukin-2
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Milk Proteins
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Morpholines
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Proto-Oncogene Proteins
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Receptors, Interleukin-2
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STAT3 Transcription Factor
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STAT3 protein, human
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STAT5 Transcription Factor
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Stat3 protein, mouse
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Trans-Activators
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Viral Fusion Proteins
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bcl-Associated Death Protein
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hemagglutinin protein G, measles virus
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Protein-Tyrosine Kinases
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JAK1 protein, human
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JAK3 protein, human
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Jak1 protein, mouse
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Jak3 protein, mouse
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Janus Kinase 1
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Janus Kinase 3
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Wortmannin