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

Ruma Mukerjee, J. Robert Chang, Luis Del Valle, Asen Bagashev, Monika M. Gayed, Randolph B. Lyde, Brian J. Hawkins, Eugen Brailoiu, Eric Cohen, Chris Power, S. Ausim Azizi, Benjamin B. Gelman, Bassel E. Sawaya

Research output: Contribution to journalArticle

31 Scopus citations

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 vsynaptic 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.

Original languageEnglish (US)
Pages (from-to)34976-34985
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number40
DOIs
StatePublished - Oct 7 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders'. Together they form a unique fingerprint.

  • Cite this

    Mukerjee, R., Chang, J. R., Del Valle, L., Bagashev, A., Gayed, M. M., Lyde, R. B., Hawkins, B. J., Brailoiu, E., Cohen, E., Power, C., Azizi, S. A., Gelman, B. B., & Sawaya, B. E. (2011). Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders. Journal of Biological Chemistry, 286(40), 34976-34985. https://doi.org/10.1074/jbc.M111.241547