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| Status |
Public on Feb 12, 2013 |
| Title |
HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs. |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus; Human alphaherpesvirus 1; Human betaherpesvirus 5; Murid betaherpesvirus 1; human gammaherpesvirus 4; JC polyomavirus; Human immunodeficiency virus 1; synthetic construct; Murid gammaherpesvirus 4; Human gammaherpesvirus 8; Betapolyomavirus hominis; Betapolyomavirus macacae |
| Sample organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Non-coding RNA profiling by array
|
| Summary |
Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release from the infected cells and taken up by noninfected cells. Using microRNA array assay, we demonstrated that Tat deregulates the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a target genes such as CREB protein as shown by real time PCR. The effect of Tat was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increase in Tat transgenic mice when compared with the parental mice. Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent.
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| Overall design |
Using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs and mRNAs.
Human fetal neurons were chosen to examine the impact of HIV-1 Tat protein on gene expression [GSM1173253-GSM1173256]
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| Contributor(s) |
Chang JR, Mukerjee R, Bagashev A, Del Valle L, Chabrashvili T, Hawkins BJ, He JJ, Sawaya BE |
| Citation(s) |
21956116 |
| |
| Submission date |
Feb 12, 2013 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Bassel E Sawaya |
| E-mail(s) |
sawaya@temple.edu
|
| Phone |
2157075446
|
| Organization name |
Temple University
|
| Department |
Neurology
|
| Street address |
3307 N. Broad Street
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19140 |
| Country |
USA |
| |
|
| Platforms (5)
|
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
| GPL8227 |
Agilent-019118 Human miRNA Microarray 2.0 G4470B (miRNA ID version) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
| GPL16346 |
miRCURY LNA microRNA Array, v.11.0 - hsa, mmu & rno [full array] |
| GPL16384 |
[miRNA-3] Affymetrix Multispecies miRNA-3 Array |
|
| Samples (32)
|
| GSM1039744 |
HIV-1 Tat (2)_HN [mRNA] |
| GSM1045805 |
Differentiated SH-5Y cells (1) [mRNA] |
| GSM1045806 |
Differentiated SH-5Y cells (2) [mRNA] |
| GSM1045807 |
Differentiated SH-5Y cells treated with supernatant from HIV-infected U-937 (1) [mRNA] |
| GSM1045808 |
Differentiated SH-5Y cells treated with supernatant from HIV-infected U-937 (2) [mRNA] |
| GSM1047649 |
Control (1)_HN [miRNA] |
| GSM1047650 |
Control (2)_HN [miRNA] |
| GSM1047651 |
HIV-1 Tat (1)_HN [miRNA] |
| GSM1047652 |
HIV-1 Tat (2)_HN [miRNA] |
| GSM1047655 |
Neurons treated with supernatant prepared from U-9367-infected with JR-FL strain of HIV-1 (1) [miRNA] |
| GSM1047656 |
Neurons treated with supernatant prepared from U-9367-infected with JR-FL strain of HIV-1 (2) [miRNA] |
| GSM1064970 |
Differentiated SH-5Y cells_Mock (1)[mRNA] |
| GSM1064971 |
Differentiated SH-5Y cells_Mock (2)[mRNA] |
| GSM1064972 |
Differentiated SH-5Y cells treated with HIV-1 tat (1)[mRNA] |
| GSM1064973 |
Differentiated SH-5Y cells treated with HIV-1 tat (2)[mRNA] |
| GSM1079086 |
Primary human Neurons_Control M1 [miRNA] |
| GSM1079087 |
Primary human Neurons_Control M2 [miRNA] |
| GSM1079088 |
Primary human Neurons_HIV-1 Tat (T1) [miRNA] |
| GSM1079089 |
Primary human Neurons_HIV-1 Tat (T2) [miRNA] |
| GSM1079608 |
Control M1_SH-SY5Y [miRNA] |
| GSM1079609 |
Control M2_SH-SY5Y [miRNA] |
| GSM1079612 |
HIV-1 Tat (T1)_SH-SY5Y [miRNA] |
| GSM1079613 |
HIV-1 Tat (T2)_SH-SY5Y [miRNA] |
| GSM1173253 |
Control M1 [miRNA] |
| GSM1173254 |
Control M2 [miRNA] |
| GSM1173255 |
HIV-1 Tat (T1) [miRNA] |
| GSM1173256 |
HIV-1 Tat (T2) [miRNA] |
| GSM1195549 |
Mock SH-SY5Y (miRNA) |
| GSM1195601 |
HIV-1 Tat SH-SY5Y (miRNA) |
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| Relations |
| BioProject |
PRJNA189269 |
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