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    Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

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    Type
    Article
    Authors
    Najera, Julia A.
    Bustamante, Eduardo A.
    Bortell, Nikki
    Morsey, Brenda
    Fox, Howard S.
    Ravasi, Timothy cc
    Marcondes, Maria Cecilia Garibaldi
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Division of Chemical & Life Sciences and Engineering
    Date
    2016-04-23
    Online Publication Date
    2016-04-23
    Print Publication Date
    2016-12
    Permanent link to this record
    http://hdl.handle.net/10754/606975
    
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    Abstract
    Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.
    Citation
    Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets 2016, 17 (1) BMC Immunology
    Sponsors
    The authors would like to thank Marcia McRae and Floriska Chizer for administrative assistance, Dr. Merhdad Alirezai for the help with microscope images, and Dr. Lindsay Whitton (TSRI), for allowing us to use his microscope. This is the manuscript number #29061 of The Scripps Research Institute. This study was funded by NIH grants 5R21DA029491 and 1R01DA036164.
    Publisher
    Springer Nature
    Journal
    BMC Immunology
    DOI
    10.1186/s12865-016-0145-0
    PubMed ID
    27107567
    Additional Links
    http://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-016-0145-0
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    • [Dataset]
      Najera, J., Bustamante, E., Bortell, N., Morsey, B., Fox, H., Ravasi, T., & Marcondes, M. (2016). Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets. Figshare. https://doi.org/10.6084/m9.figshare.c.3611954. DOI: 10.6084/m9.figshare.c.3611954 HANDLE: 10754/624130
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12865-016-0145-0
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program

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