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| Status |
Public on Feb 12, 2013 |
| Title |
Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders. |
| 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; 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
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| Summary |
Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders.
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| Overall design |
Using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Vpr) on the expression of miRNAs and mRNAs.
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| Contributor(s) |
Mukerjee R, Chang JR, Del Valle L, Bagashev A, Gayed MM, Lyde RB, Hawkins BJ, Brailoiu E, Cohen E, Power C, Azizi SA, Gelman BB, Sawaya BE |
| Citation(s) |
21816823 |
| |
| Submission date |
Feb 12, 2013 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Bassel E Sawaya |
| E-mail(s) |
sawaya@temple.edu
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| Phone |
2157075446
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| Organization name |
Temple University
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| Department |
Neurology
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| Street address |
3307 N. Broad Street
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19140 |
| Country |
USA |
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| Platforms (4)
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| 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] |
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| Samples (28)
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| GSM1039746 |
HIV-1 Vpr (2) [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] |
| GSM1047653 |
HIV-1 Vpr (1) [miRNA] |
| GSM1047654 |
HIV-1 Vpr (2) [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] |
| GSM1064974 |
Differentiated SH-5Y cells_Mock-(1)[mRNA] |
| GSM1064975 |
Differentiated SH-5Y cells_Mock-(2)[mRNA] |
| GSM1064976 |
Differentiated SH-5Y cells treated with HIV-1 Vpr (1)[mRNA] |
| GSM1064977 |
Differentiated SH-5Y cells treated with HIV-1 Vpr (2)[mRNA] |
| GSM1079562 |
Control M1 [miRNA] |
| GSM1079563 |
Control M2 [miRNA] |
| GSM1079564 |
HIV-1 Vpr (V1) [miRNA] |
| GSM1079565 |
HIV-1 Vpr (V2) [miRNA] |
| GSM1079566 |
HIV-1 Vpr_HN [miRNA] |
| GSM1079567 |
Control_HN [miRNA] |
| GSM1079610 |
HIV-1 Vpr (V1)_SH-SY5Y [miRNA] |
| GSM1079611 |
HIV-1 Vpr (V2)_SH-SY5Y [miRNA] |
| GSM1195549 |
Mock SH-SY5Y (miRNA) |
| GSM1195550 |
HIV-1 Vpr SH-SY5Y (miRNA) |
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| Relations |
| BioProject |
PRJNA189270 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44266_RAW.tar |
59.7 Mb |
(http)(custom) |
TAR (of CEL, GPR, TXT) |
| Processed data included within Sample table |
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