title: Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection.
abstract: 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 disintegrins and metalloproteinases with thrombospondin 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.
authors.affiliation: Division of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Medina-Flores
authors.forename: Guoji
authors.initials: G
authors.lastname: Wang
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bissel
authors.forename: Michael
authors.initials: M
authors.lastname: Murphey-Corb
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
mesh_terms: D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019483:Disintegrins / Q000378:metabolism; D018792:Encephalitis, Viral / Q000378:metabolism / Q000473:pathology; D010450:Endopeptidases / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008666:Metalloendopeptidases / Q000378:metabolism; D037121:Plant Lectins; D011348:Procollagen N-Endopeptidase; D011509:Proteoglycans / Q000378:metabolism*; D034781:Receptors, N-Acetylglucosamine; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology*; D015302:Simian Immunodeficiency Virus; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019483:Disintegrins; D010450:Endopeptidases; D016326:Extracellular Matrix Proteins; D008666:Metalloendopeptidases; D037121:Plant Lectins; D011348:Procollagen N-Endopeptidase; D011509:Proteoglycans; D034781:Receptors, N-Acetylglucosamine; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C040129:wisteria lectin; C000603918:ADAMTS4 protein, human; C083641:aggrecanase