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| Status |
Public on Jan 29, 2010 |
| Title |
Profiling of genes deregulated in CD4+ T cells expressing constitutively full-length or first-exon Tat protein of HIV-1 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Background: The role of HIV-1 Tat protein in gene expression deregulation and functional biology of CD4+ T lymphocytes was analyzed, as well as the function of Tat second exon for the complete activity of this protein. Gene expression deregulation profiles of triplicate samples from Jurkat cells expressing intracellular full-length Tat (1-101aa) in comparison with a truncated form lacking the second exon (1-72aa) was evaluated by bioinformatics using whole human genome microarrays. Results: More than 1000 genes were deregulated in Jurkat Tat101 cells, whereas less than 300 genes were deregulated in Jurkat Tat72 cells (q-value<5%; fold change >2 or <-2). Ontological analysis indicated that several functions were impaired mainly in Jurkat Tat101 as cellular movement, growth and proliferation, cell-to-cell signaling, molecular transport, cell death, cell morphology, and T-cell activation. In accordance, biological and functional analyses proved that Tat101 intracellular expression induced changes in cell size and complexity, cytoskeletal rearrangements and chemotaxis impairment, higher resistance to apoptosis, decrease in the surface expression of adhesion molecules and receptors, and higher basal transcriptional activation. These alterations were attenuated or absent in Jurkat Tat72 cells. Furthermore, computational modeling showed that the absence of second exon severely reduced the C-terminus of Tat72 with notable decrease of positive charging. Conclusion: Full-length Tat intracellular expression induced dramatic structural changes and impaired essential functions in CD4+ T cells, whereas Tat72 was less aggressive. Consequently, although Tat first exon is transcriptionally autonomous, second exon should be indispensable for triggering HIV-1 pathogenic events induced by Tat protein.
Keywords: Microarray Genome-wide expression analysis. Comparison of genetically modified cells
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| Overall design |
Total RNA was obtained from Jurkat cell lines that express constitutively intracellular HIV-1 Tat101 or Tat72. Gene expression profiles were obtained for each sample and compared with a parental Jurkat cell line that does not express Tat.
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| Contributor(s) |
López-Huertas M, Callejas S, Abia D, Dopazo A, Alcamí J, Coiras M |
| Citation(s) |
20139419 |
| Submission date |
Jan 28, 2010 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Sergio Callejas |
| Organization name |
Centro Nacional de Investigaciones Cardiovasculares (CNIC)
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| Department |
Genomics Unit
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| Lab |
Genomics Unit
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| Street address |
Melchor Fernández Almagro, 3
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| City |
Madrid |
| ZIP/Postal code |
28029 |
| Country |
Spain |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA124289 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE20088_RAW.tar |
47.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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