|
| Status |
Public on Dec 31, 2015 |
| Title |
HIV-1 TAT SUPPRESSES THE TCR/CD3 MACHINERY IN HUMAN CD4+ T CELLS |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Our previous work demonstrated that HIV-1 infection progressively reduces TCR/CD3 expression due to a defect in CD3g gene transcripts. We further found that knocking down expression of the viral tat and/or nef genes was correlated with CD3g transcript and TCR/CD3 surface receptor levels on HIV-1 infected cells. This study was undertaken to investigate the direct effect of HIV-1 Tat expression on the TCR/CD3 machinery. Progressive downregulation from TCR/CD3hi to TCR/CD3lo to TCR/CD3? was observed on Tat expressing cells in a manner that emulated HIV-1 infection, with a lack of CD3g transcripts again responsible for the defect. When Tat cell cultures containing a mixture of TCR/CD3 surface densities were separated into TCR/CD3hi and TCR/CD3lo/? populations, they quickly reverted to a mixed CD3 phenotype. Thus, the progression TCR/CD3hi to TCR/CD3lo to TCR/CD3? is an active, reversible process with receptor levels fluctuating in response to intracellular dynamics. Examination of tat mutants found that the regions involved in Tat-mediated transactivation and TAR binding are required for TCR/CD3 downregulation while the lysine at position 28 and Tat exon 2 are dispensable. Global gene expression, assessed in association with TCR/CD3 downregulation in HIV-1 infected and Tat expressing cells, detected broad suppression of TCR/CD3 signaling, co-stimulation and negative regulatory genes along with target transcription factors, ligands and receptors. A significant subset of the genes altered in HIV-1 infected cells was specifically targeted by Tat in association with TCR/CD3 loss. Our finding that Tat negatively regulates many facets of the TCR/CD3 machinery has important implications for disease pathogenesis.
This SuperSeries is composed of the SubSeries listed below.
|
| |
|
| Overall design |
Refer to individual Series
|
| |
|
| Contributor(s) |
Willard-Gallo K |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Oct 05, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Chunyan GU |
| E-mail(s) |
chunyan.gu@bordet.be
|
| Phone |
+32(0)25413711
|
| Organization name |
Free University of Brussels
|
| Department |
Medecine (Jules Bordet Institute)
|
| Lab |
Molecular Immunology
|
| Street address |
Bld de Waterloo 127
|
| City |
Brussels |
| ZIP/Postal code |
1000 |
| Country |
Belgium |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (10)
|
|
| This SuperSeries is composed of the following SubSeries: |
| GSE33705 |
HIV-1 TAT SUPPRESSES THE TCR/CD3 MACHINERY IN HUMAN CD4+ T CELLS [Tat] |
| GSE33706 |
HIV-1 TAT SUPPRESSES THE TCR/CD3 MACHINERY IN HUMAN CD4+ T CELLS [HIV] |
|
| Relations |
| BioProject |
PRJNA147803 |
Less...
More...