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 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 aisintegrins and metalloproteinases with thrombogpondin 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 proteoglyeans might avert or delay retroviral-induced neurodegeneration. (C) 2004 Elsevier Inc. All rights reserved.