Transcriptomics

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13

Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders.


ABSTRACT: 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. 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: C Power   S A Azizi  Bassel E Sawaya  M M Gayed  R B Lyde  B B Gelman  E Cohen  J R Chang  R Mukerjee  B J Hawkins  B E Sawaya  E Brailoiu 

PROVIDER: E-GEOD-44266 | ArrayExpress | 2013-02-12

SECONDARY ACCESSION(S): GSE44266PRJNA189270

REPOSITORIES: GEO, ArrayExpress

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Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders.

Mukerjee Ruma R   Chang J Robert JR   Del Valle Luis L   Bagashev Asen A   Gayed Monika M MM   Lyde Randolph B RB   Hawkins Brian J BJ   Brailoiu Eugen E   Cohen Eric E   Power Chris C   Azizi S Ausim SA   Gelman Benjamin B BB   Sawaya Bassel E BE  

The Journal of biological chemistry 20110804 40


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 ce  ...[more]

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