title: Disruption of Akt kinase activation is important for immunosuppression induced by measles virus.
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.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Avota
authors.forename: A
authors.initials: A
authors.lastname: Avots
authors.forename: S
authors.initials: S
authors.lastname: Niewiesk
authors.forename: L P
authors.initials: LP
authors.lastname: Kane
authors.forename: U
authors.initials: U
authors.lastname: Bommhardt
authors.forename: V
authors.initials: V
authors.lastname: ter Meulen
authors.forename: S
authors.initials: S
authors.lastname: Schneider-Schaulies
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D008213:Lymphocyte Activation; D008457:Measles / Q000276:immunology* / Q000821:virology; D008459:Measles virus / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins; D009025:Morpholines / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D016205:Sigmodontinae; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000378:metabolism; D000077191:Wortmannin; D051025:bcl-Associated Death Protein
chemical_list: D000730:Androstadienes; C494819:BAD protein, human; C494820:Bad protein, mouse; D002352:Carrier Proteins; D002867:Chromones; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006389:Hemagglutinins, Viral; D007376:Interleukin-2; D008894:Milk Proteins; D009025:Morpholines; D011518:Proto-Oncogene Proteins; D015375:Receptors, Interleukin-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014760:Viral Fusion Proteins; D051025:bcl-Associated Death Protein; C032397:hemagglutinin protein G, measles virus; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; C507905:Jak1 protein, mouse; C507935:Jak3 protein, mouse; D053613:Janus Kinase 1; D053616:Janus Kinase 3; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin