Filtern
Volltext vorhanden
- ja (31)
Gehört zur Bibliographie
- ja (31)
Erscheinungsjahr
Dokumenttyp
Schlagworte
- Virologie (11)
- measles virus (5)
- sphingomyelinase (4)
- Immunologie (3)
- Masernvirus (3)
- SARS-CoV-2 (3)
- ceramides (3)
- Biologie (2)
- T cell receptors (2)
- T cells (2)
- dendritic cell (2)
- flow cytometry (2)
- 3D tissue model (1)
- ATP-adenosine triphosphate (1)
- CNS infection (1)
- Dendritische Zelle (1)
- Escherichia coli infections (1)
- HIV (1)
- Immunbiologie (1)
- LFA-1 (1)
- MV receptor (1)
- MV transcription (1)
- Masern (1)
- Medicine (1)
- Medizin (1)
- Mitochondria (1)
- Neisseria meningitidis (1)
- Ratte (1)
- Seahorse XF (1)
- T cell (1)
- T cell migration (1)
- T cell receptor (1)
- T cell silencing (1)
- TCR signaling cascade (1)
- Zentralnervensystem (1)
- acid sphingomyelinase (1)
- actins (1)
- activation (1)
- adhesion (1)
- alternative splicing (1)
- azido-ceramides (1)
- bacterial pathogens (1)
- cell cycle and cell division (1)
- cell membrane (1)
- cell migration (1)
- cell staining (1)
- ceramidase (1)
- ceramide (1)
- cytoskeleton (1)
- endothelial cells (1)
- enzymes (1)
- fluoxetine (1)
- gene regulation (1)
- genetic interference (1)
- glycosphingolipids (1)
- immunosuppression (1)
- measles (1)
- meningococcal disease (1)
- motility (1)
- neutral sphingomyelinase (1)
- neutral sphingomyelinase-2 (1)
- oxidative phosphorylation (1)
- polarization (1)
- reverse transcriptase-polymerase chain reaction (1)
- small interfering RNAs (1)
- sphingolipids (1)
- sphingosine 1-phosphate (1)
- sphingosine-1-phosphate (1)
- tyrosine (1)
- unwindase (1)
Background
Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA.
Hypothesis
Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing.
Methods
To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression.
Results
Applying our algorithm to the data, 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry.
Conclusions
PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression.
Background: Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis: Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. Methods: To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. Results: Applying our algorithm to the data, 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. Conclusions: PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression.
Human immunodeficiency virus (HIV-1) infection in the human brain Ieads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp 120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on int~acellular.s.ignallin~. Herewe pre~ent evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatlde, spec1f1cally bmds to a protem receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) pre~ent. on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rap1dly 1nduced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130- and 115-kDa p~oteins. The c~ncentration of intracellular calciumwas not affected by rgp120 in these cells. Our data suggest a novel Signal transduc1ng HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.