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

Handle URI:
http://hdl.handle.net/10754/606975
Title:
Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets
Authors:
Najera, Julia A.; Bustamante, Eduardo A.; Bortell, Nikki; Morsey, Brenda; Fox, Howard S.; Ravasi, Timothy ( 0000-0002-9950-465X ) ; Marcondes, Maria Cecilia Garibaldi
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.
KAUST Department:
Division of Chemical & Life Sciences and Engineering
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
Publisher:
Springer Science + Business Media
Journal:
BMC Immunology
Issue Date:
23-Apr-2016
DOI:
10.1186/s12865-016-0145-0
Type:
Article
ISSN:
1471-2172
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.
Is Supplemented By:
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:http://hdl.handle.net/10754/624130
Additional Links:
http://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-016-0145-0
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorNajera, Julia A.en
dc.contributor.authorBustamante, Eduardo A.en
dc.contributor.authorBortell, Nikkien
dc.contributor.authorMorsey, Brendaen
dc.contributor.authorFox, Howard S.en
dc.contributor.authorRavasi, Timothyen
dc.contributor.authorMarcondes, Maria Cecilia Garibaldien
dc.date.accessioned2016-04-25T13:59:33Zen
dc.date.available2016-04-25T13:59:33Zen
dc.date.issued2016-04-23en
dc.identifier.citationMethamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets 2016, 17 (1) BMC Immunologyen
dc.identifier.issn1471-2172en
dc.identifier.doi10.1186/s12865-016-0145-0en
dc.identifier.urihttp://hdl.handle.net/10754/606975en
dc.description.abstractBackground 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.en
dc.description.sponsorshipThe 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.en
dc.language.isoenen
dc.publisherSpringer Science + Business Mediaen
dc.relation.urlhttp://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-016-0145-0en
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.en
dc.subjectMethamphetamineen
dc.subjectNeuroAIDSen
dc.subjectMicrogliaen
dc.subjectCCR5en
dc.subjectSimian immunodeficiency virusen
dc.subjectHuman immunodeficiency virusen
dc.subjectBrainen
dc.subjectCentral nervous systemen
dc.subjectInflammationen
dc.titleMethamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targetsen
dc.typeArticleen
dc.contributor.departmentDivision of Chemical & Life Sciences and Engineeringen
dc.identifier.journalBMC Immunologyen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCellular and Molecular Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Rd. SR307, La Jolla, CA 92037, USAen
dc.contributor.institutionDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5800, USAen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorRavasi, Timothyen
dc.relation.isSupplementedByNajera, 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.3611954en
dc.relation.isSupplementedByDOI:10.6084/m9.figshare.c.3611954en
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624130en
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