Dataset Information


Profiling of genes deregulated in CD4+ T cells expressing constitutively full-length or first-exon Tat protein of HIV-1

ABSTRACT: 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 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.

INSTRUMENT(S): Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)

SUBMITTER: Sergio Callejas 

PROVIDER: GSE20088 | GEO | 2010-01-29



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Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon.

López-Huertas M R MR   Callejas S S   Abia D D   Mateos E E   Dopazo A A   Alcamí J J   Coiras M M  

Nucleic acids research 20100205 10

The human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apoptosis. In contrast, intracellular Tat has been described as protector from apoptosis. Tat gene is composed by two coding exons that yield a protein of 101 amino acids (aa). First exon (1-72aa) is suf  ...[more]

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