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

Authors

Ruma Mukerjee, Temple University School of Medicine - Philadelphia
J Robert Chang, Temple University School of Medicine - Philadelphia
Luis Del Valle, LSU Health Sciences Center - New OrleansFollow
Asen Bagashev, Temple University School of Medicine - Philadelphia
Monika M. Gayed, Temple University School of Medicine - Philadelphia
Randolph B. Lyde, Temple University School of Medicine - Philadelphia
Brian J. Hawkins, University of Washington - Seattle
Eugen Brailoiu, Temple University School of Medicine - Philadelphia
Eric Cohen, Université de Montréal - Quebec, Canada
Chris Power, University of Alberta - Edmunton, Alberta, Canada
S Ausim Azizi, Temple University School of Medicine - Philadelphia
Benjamin B. Gelman, University of Texas Medical Branch - Galveston, TX
Bassel E. Sawaya, Temple University School of Medicine - Philadelphia

Document Type

Article

Publication Date

10-7-2011

Publication Title

The Journal of Biological Chemistry

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.

First Page

34976

Last Page

85

PubMed ID

21816823

Volume

286

Issue

40

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Mukerjee, Ruma; Chang, J Robert; Del Valle, Luis; Bagashev, Asen; Gayed, Monika M.; Lyde, Randolph B.; Hawkins, Brian J.; Brailoiu, Eugen; Cohen, Eric; Power, Chris; Azizi, S Ausim; Gelman, Benjamin B.; and Sawaya, Bassel E., "Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders" (2011). School of Medicine Faculty Publications. 2330.
https://digitalscholar.lsuhsc.edu/som_facpubs/2330