Journal of NeuroVirology

, Volume 18, Issue 5, pp 400–410

Methamphetamine activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induces human immunodeficiency virus (HIV) transcription in human microglial cells

  • Emily S. Wires
  • David Alvarez
  • Curtis Dobrowolski
  • Yun Wang
  • Marisela Morales
  • Jonathan Karn
  • Brandon K. Harvey
Article

DOI: 10.1007/s13365-012-0103-4

Cite this article as:
Wires, E.S., Alvarez, D., Dobrowolski, C. et al. J. Neurovirol. (2012) 18: 400. doi:10.1007/s13365-012-0103-4

Abstract

Human immunodeficiency virus (HIV) primarily infects glial cells in the central nervous system (CNS). Recent evidence suggests that HIV-infected individuals who abuse drugs such as methamphetamine (METH) have higher viral loads and experience more severe neurological complications than HIV-infected individuals who do not abuse drugs. The aim of this study was to determine the effect of METH on HIV expression from the HIV long terminal repeat (LTR) promoter and on an HIV integrated provirus in microglial cells, the primary host cells for HIV in the CNS. Primary human microglial cells immortalized with SV40 T antigen (CHME-5 cells) were cotransfected with an HIV LTR reporter and the HIV Tat gene, a key regulator of viral replication and gene expression, and exposed to METH. Our results demonstrate that METH treatment induced LTR activation, an effect potentiated in the presence of Tat. We also found that METH increased the nuclear translocation of the nuclear factor kappa B (NF-κB), a key cellular transcriptional regulator of the LTR promoter, and the activity of an NF-κB-specific reporter plasmid in CHME-5 cells. The presence of a dominant-negative regulator of NF-κB blocked METH-related activation of the HIV LTR. Furthermore, treatment of HIV-latently infected CHME-5 (CHME-5/HIV) cells with METH induced HIV expression and nuclear translocation of the p65 subunit of NF-κB. These results suggest that METH can stimulate HIV gene expression in microglia cells through activation of the NF-κB signaling pathway. This mechanism may outline the initial biochemical events leading to the observed increased neurodegeneration in HIV-positive individuals who use METH.

Keywords

HIV Microglia Methamphetamine NF-kappa B (NF-κB) Nuclear translocation 

Supplementary material

13365_2012_103_MOESM1_ESM.pdf (17.4 mb)
ESM 1(PDF 17864 kb)
13365_2012_103_MOESM2_ESM.pdf (7.4 mb)
ESM 2(PDF 7606 kb)

Copyright information

© Journal of NeuroVirology, Inc. (outside the USA) 2012

Authors and Affiliations

  • Emily S. Wires
    • 1
  • David Alvarez
    • 2
  • Curtis Dobrowolski
    • 2
  • Yun Wang
    • 1
  • Marisela Morales
    • 1
  • Jonathan Karn
    • 2
  • Brandon K. Harvey
    • 1
  1. 1.Intramural Research Program, National Institute on Drug AbuseNational Institutes of HealthBaltimoreUSA
  2. 2.Department of Molecular Biology and MicrobiologyCase Western Reserve UniversityClevelandUSA

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