HIV-1 INDUCED DESTRUCTION OF NEOCORTICAL EXTRACELLULAR-MATRIX COMPONENTS IN AIDS VICTIMS

Neurological dysfunction is not uncommon in patients suffering from ac quired immunodeficiency syndrome (AIDS) and, when manifested, intimate s involvement of the central nervous system. Here, the human immunodef iciency virus (HIV) infects preferentially microglial cells, which the reby release substances known to interfere with neuronal function. One class of agents set free in this manner are proteases; these degrade certain components within, and thereby undermine the integrity of, the extracellular matrix (ECM) compartment, which plays a vital role in c ell-to-cell communication. We wished to ascertain whether the ECM comp artment is indeed disrupted in the brains of AIDS victims. We examined the neocortical areas of 27 AIDS autopsy cases, including 9 with diag nosed HIV-encephalopathy (HIVE); 8 HIV-seronegative cases with various types of brain lesion, including viral infections, were also included in this study. HIV-antigens and DNA were identified by use of immunoh istochemistry and in situ hybridization, and ECM components by lectin staining and immunohistochemistry. Of the 27 AIDS cases examined, each of the 9 with HIVE was completely devoid of labeled ECM components; 8 of the 18 without HIVE had incurred substantial losses, and only 2 ma nifested a normal complement of constituents within this compartment W ith respect to stratal and topographic variations, layers II and III w ere less affected than layers V to VII, as was the frontal cortex rela tive to other areas. These findings confirmed our expectations of the brain's ECM undergoing degradation following HIV infection, and these changes may well underlie the neurological disturbances manifested in AIDS patients. (C) 1997 Academic Press.