Supplementary Material for: 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/10754/624130
Title:
Supplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets
Authors:
Najera, Julia; Bustamante, Eduardo; Bortell, Nikki; Morsey, Brenda; Fox, Howard; Ravasi, Timothy ( 0000-0002-9950-465X ) ; Marcondes, Maria
Abstract:
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:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
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
Publisher:
Figshare
Issue Date:
2016
DOI:
10.6084/m9.figshare.c.3611954
Type:
Dataset
Is Supplement To:
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; DOI:10.1186/s12865-016-0145-0; HANDLE:http://hdl.handle.net/10754/606975
Appears in Collections:
Datasets; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorNajera, Juliaen
dc.contributor.authorBustamante, Eduardoen
dc.contributor.authorBortell, Nikkien
dc.contributor.authorMorsey, Brendaen
dc.contributor.authorFox, Howarden
dc.contributor.authorRavasi, Timothyen
dc.contributor.authorMarcondes, Mariaen
dc.date.accessioned2017-06-06T07:44:32Z-
dc.date.available2017-06-06T07:44:32Z-
dc.date.created2016-12-14en
dc.date.issued2016en
dc.identifier.citationNajera, 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.identifier.doi10.6084/m9.figshare.c.3611954en
dc.identifier.urihttp://hdl.handle.net/10754/624130-
dc.description.abstractAbstract 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.en
dc.publisherFigshareen
dc.rightsCC BYen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectMedicineen
dc.subjectNeuroscienceen
dc.subjectPharmacologyen
dc.subjectBiotechnologyen
dc.subjectImmunologyen
dc.subjectCanceren
dc.subjectMental Healthen
dc.subjectInfectious Diseasesen
dc.subjectVirologyen
dc.titleSupplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targetsen
dc.typeDataseten
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
kaust.authorRavasi, Timothyen
dc.type.resourceCollectionen
dc.relation.isSupplementToMethamphetamine 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.relation.isSupplementToDOI:10.1186/s12865-016-0145-0en
dc.relation.isSupplementToHANDLE:http://hdl.handle.net/10754/606975en
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