Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection

Disruption of the perineuronal matrix has been reported in human immunodeficiency virus (HIV) encephalitis. To better understand the extent of matrix disruption during lentiviral encephalitis, we characterized the extracellular matrix (ECM) damage in brains of 12 macaques infected with simian immuno...

Full description

Bibliographic Details
Main Authors: Rafael Medina-Flores, Guoji Wang, Stephanie J Bissel, Michael Murphey-Corb, Clayton A Wiley
Format: Article
Language:English
Published: Elsevier 2004-08-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996104001044
_version_ 1818417445658951680
author Rafael Medina-Flores
Guoji Wang
Stephanie J Bissel
Michael Murphey-Corb
Clayton A Wiley
author_facet Rafael Medina-Flores
Guoji Wang
Stephanie J Bissel
Michael Murphey-Corb
Clayton A Wiley
author_sort Rafael Medina-Flores
collection DOAJ
description Disruption of the perineuronal matrix has been reported in human immunodeficiency virus (HIV) encephalitis. To better understand the extent of matrix disruption during lentiviral encephalitis, we characterized the extracellular matrix (ECM) damage in brains of 12 macaques infected with simian immunodeficiency virus (SIV). Matrix integrity was assessed by Wisteria floribunda lectin histochemistry. Confocal microscopy was used to quantify matrix loss, macrophage infiltration, and synaptic damage. Disruption of brain ECM was present shortly after retroviral infection, preceding parenchymal macrophage infiltration. In agreement with previous observations, reduced staining of presynaptic and postsynaptic proteins in SIV encephalitis occurred concurrently with matrix abnormalities. Lentiviral infection induced microglial and macrophage expression of two ḏisintegrins and m̱etalloproteinases with ṯhrombos̱pondin motifs (ADAMTS-1 and ADAMTS-4), with high substrate specificity for matrix proteoglycans. Matrix damage is pervasive during SIV neuroinfection, which suggests interventions to conserve brain matrix proteoglycans might avert or delay retroviral-induced neurodegeneration.
first_indexed 2024-12-14T12:06:54Z
format Article
id doaj.art-9a5683efa9654a13a9e24251ad32313d
institution Directory Open Access Journal
issn 1095-953X
language English
last_indexed 2024-12-14T12:06:54Z
publishDate 2004-08-01
publisher Elsevier
record_format Article
series Neurobiology of Disease
spelling doaj.art-9a5683efa9654a13a9e24251ad32313d2022-12-21T23:01:50ZengElsevierNeurobiology of Disease1095-953X2004-08-01163604616Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfectionRafael Medina-Flores0Guoji Wang1Stephanie J Bissel2Michael Murphey-Corb3Clayton A Wiley4Division of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213, USADivision of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213, USADivision of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213, USADivision of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213, USADivision of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213, USADisruption of the perineuronal matrix has been reported in human immunodeficiency virus (HIV) encephalitis. To better understand the extent of matrix disruption during lentiviral encephalitis, we characterized the extracellular matrix (ECM) damage in brains of 12 macaques infected with simian immunodeficiency virus (SIV). Matrix integrity was assessed by Wisteria floribunda lectin histochemistry. Confocal microscopy was used to quantify matrix loss, macrophage infiltration, and synaptic damage. Disruption of brain ECM was present shortly after retroviral infection, preceding parenchymal macrophage infiltration. In agreement with previous observations, reduced staining of presynaptic and postsynaptic proteins in SIV encephalitis occurred concurrently with matrix abnormalities. Lentiviral infection induced microglial and macrophage expression of two ḏisintegrins and m̱etalloproteinases with ṯhrombos̱pondin motifs (ADAMTS-1 and ADAMTS-4), with high substrate specificity for matrix proteoglycans. Matrix damage is pervasive during SIV neuroinfection, which suggests interventions to conserve brain matrix proteoglycans might avert or delay retroviral-induced neurodegeneration.http://www.sciencedirect.com/science/article/pii/S0969996104001044SIVHIV-1AIDSEncephalitisExtracellular matrixProteoglycans
spellingShingle Rafael Medina-Flores
Guoji Wang
Stephanie J Bissel
Michael Murphey-Corb
Clayton A Wiley
Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection
Neurobiology of Disease
SIV
HIV-1
AIDS
Encephalitis
Extracellular matrix
Proteoglycans
title Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection
title_full Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection
title_fullStr Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection
title_full_unstemmed Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection
title_short Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection
title_sort destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection
topic SIV
HIV-1
AIDS
Encephalitis
Extracellular matrix
Proteoglycans
url http://www.sciencedirect.com/science/article/pii/S0969996104001044
work_keys_str_mv AT rafaelmedinaflores destructionofextracellularmatrixproteoglycansispervasiveinsimianretroviralneuroinfection
AT guojiwang destructionofextracellularmatrixproteoglycansispervasiveinsimianretroviralneuroinfection
AT stephaniejbissel destructionofextracellularmatrixproteoglycansispervasiveinsimianretroviralneuroinfection
AT michaelmurpheycorb destructionofextracellularmatrixproteoglycansispervasiveinsimianretroviralneuroinfection
AT claytonawiley destructionofextracellularmatrixproteoglycansispervasiveinsimianretroviralneuroinfection