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.
Subject(s)
Immune Tolerance , Measles virus/immunology , Measles/immunology , Milk Proteins , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins/metabolism , Receptors, Interleukin-2/metabolism , Signal Transduction/physiology , T-Lymphocytes/immunology , Androstadienes/pharmacology , Animals , Apoptosis/drug effects , Carrier Proteins/metabolism , Cell Line , Chromones/pharmacology , DNA-Binding Proteins/metabolism , Enzyme Activation , Enzyme Inhibitors/pharmacology , Hemagglutinins, Viral/metabolism , Humans , Interleukin-2/metabolism , Janus Kinase 1 , Janus Kinase 3 , Lymphocyte Activation , Measles/virology , Measles virus/metabolism , Measles virus/radiation effects , Mice , Mice, Transgenic , Morpholines/pharmacology , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/immunology , Proto-Oncogene Proteins c-akt , STAT3 Transcription Factor , STAT5 Transcription Factor , Sigmodontinae , Spleen/cytology , T-Lymphocytes/enzymology , T-Lymphocytes/metabolism , Trans-Activators/metabolism , Viral Fusion Proteins/metabolism , Wortmannin , bcl-Associated Death ProteinABSTRACT
The RNA of Escherichia coli infected with RNA bacteriophage Q beta was isolated and screened for replicable short-chained RNA. In contrast to earlier assumptions we show that (i) short-chained replicable RNA is a very minor part of the RNA synthesized in the infection cycle, and (ii) that the replicable RNA isolated from infected cells is derived from cellular RNA, in particular 23 S rRNA and 10 Sa RNA, and from Q beta RNA itself. None of the many RNA species known from in vitro experiments was found. The RNA species isolated were all inefficient templates. No replicable RNA could be isolated from non-infected cells. Even in cells expressing high amounts of Q beta replicase very few RNA species could be isolated. RNA generated in vitro in template-free synthesis is therefore not derived from RNA species found in vivo, and replicable RNA found in vitro is generated by a mechanism fundamentally different from the one operating in vivo.
