FELINE IMMUNODEFICIENCY VIRUS CAUSES INCREASED GLUTAMATE LEVELS AND NEURONAL LOSS IN BRAIN

Feline immunodeficiency virus, like human immunodeficiency virus type 1, is a retrolentivirus causing neurological disease and immune suppre ssion. Primary neurological complications, including human immunodefic iency virus encephalopathy and peripheral neuropathy, and neuropatholo gical changes, including gliosis, neuronal injury and multinucleated g iant cells, have been described for human immunodeficiency virus type 1 infection. Excitatory amino acids have been implicated as a basis fo r human immunodeficiency virus encephalopathy and the accompanying neu ronal injury. Here, we lest our hypothesis that feline immunodeficienc y virus infection results in glial activation accompanied by enhanced glutamatergic activity, causing neuronal loss. Neurological signs obse rved in naturally and experimentally infected animals included ataxia, aggressivity and reduced motor activity. Neuropathological changes in cluded gliosis, perivascular cuffing and neuronal dropout in the brain s of both experimentally and naturally infected animals, but not in un infected animals. Feline immunodeficiency virus antigen and genome wer e detected in the brains of all experimentally and naturally infected animals. Proton nuclear magnetic resonance spectroscopy revealed signi ficantly increased glutamate levels in the feline immunodeficiency vir us-infected animals. In contrast, glutamate decarboxylase levels in GA BAergic neurons were reduced in feline immunodeficiency virus-infected animals. These findings provide direct in vivo evidence for enhanced glutamate levels in conjunction with neuronal loss, supporting the hyp othesis of glulamate-mediated neurotoxicity as a major mechanism in th e neuropathogenesis of retrolentiviral infections. (C) 1997 IBRO. Publ ished by Elsevier Science Ltd.