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The Coat Protein gp120 of HIV-1 Inhibits Astrocyte Uptake of Excitatory Amino Acids via Macrophage Arachidonic Acid

Authors

  • Evan B. Dreyer,

    1. Howe Laboratory, Massachusetts Eye and Ear Infirmary; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
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  • Stuart A. Lipton

    Corresponding author
    1. Laboratory of Cellular & Molecular Neuroscience, Children's Hospital; Departments of Neurology, Children's Hospital, Beth Israel Hospital, Brigham and Women's Hospital, Massachusetts General Hospital; and the Program in Neuroscience, Harvard Medical School, Boston, MA, USA
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Correspondence to: S. A. Lipton, Laboratory of Cellular & Molecular Neuroscience, Children's Hospital/Harvard Medical School, 300 Longwood Avenue-Enders Building, Suite 361, Boston, MA 02115, USA

Abstract

The human immunodeficiency virus coat protein gp120 injures central mammalian neurons both in vitro and in vivo, and this observation may contribute, at least in part, to the neurological dysfunction associated with the acquired immunodeficiency syndrome. Recent work suggests that gp 120 mediates neuronal damage predominantly via an indirect route involving activation of brain macrophages. We have previously shown that the stimulation of N-methyl-D-aspartate receptors by excitatory amino acids is essential for the neuronal injury observed with gp 120. Here we show that gp 120 impairs astrocyte uptake of excitatory amino acids and the excess glutamate thus engendered may contribute to the increased neuronal damage. We also studied the mechanism whereby gp 120 inhibits the uptake of excitatory amino acids by astrocytes. We present data suggesting that at least one pathway involves a direct effect of gp120 on macrophages, which in turn release arachidonic acid, a known inhibitor of excitatory amino acid uptake by astrocytes. Our findings suggest that the observed effects on glia and neurons of gp120 may be secondary, at least in part, to its initial activation of macrophages.

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