Human immunodeficiency virus type-1 Nef protein induces blood-brain barrier disruption in the rat: role of matrix metalloproteinase-9

We recently showed that MMP-9 activity was detectable in the cerebrospinal fluid (CSF) of about half of neurologically symptomatic HIV-infected patien ts. Using an experimental animal model, we detected MMP-9 activity in CSF s amples from rats that had been injected intracisternally with recombinant H IV-1 Nef protein, but not after injection of heat-treated Nef, gp120, gp160 or PBS. Nef also induced a breaching of the blood-brain barrier (BBB), whi ch could be inhibited by pretreatment with the matrix metalloproteinase (MM P) inhibitor batimastat. In vitro Nef only slightly induced MMP-9 activity in freshly isolated human peripheral blood mononuclear cells and in the mur ine macrophage cell line RAW 264.7, but not in endothelial, neuronal or ast roglial cell lines. Taken together, our findings indicate that HIV-1 Nef pr otein can induce BBB disruption in the rat - presumably via MMP induction. (C) 2000 Elsevier Science B.V. All rights reserved.