Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Pathol. 2014 Jan;184(1):92-100. doi: 10.1016/j.ajpath.2013.09.011. Epub 2013 Oct 26.

Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

Author information

  • 1Laboratory of Retrovirology and Epigenetics, Center for AIDS Health Disparities Research, Vanderbilt-Meharry Center for AIDS Research, Nashville, Tennessee.
  • 2Laboratory of Retrovirology and Epigenetics, Center for AIDS Health Disparities Research, Vanderbilt-Meharry Center for AIDS Research, Nashville, Tennessee; Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, Tennessee; Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: cdash@mmc.edu.

Abstract

Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis.

Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMID:
24434277
[PubMed - indexed for MEDLINE]
PMCID:
PMC3873480
[Available on 2015/1/1]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk