AN OLIGOPEPTIDE OF THE FELINE LEUKEMIA-VIRUS ENVELOPE GLYCOPROTEIN ISASSOCIATED WITH MORPHOLOGICAL-CHANGES AND CALCIUM DYSREGULATION IN NEURONAL GROWTH CONES

Neuropathogenic processes that affect the pathfinding properties of ne uronal growth cones could account for many of the dysfunctions unique to retroviral infection of developing nervous systems. Pediatric HIV-1 infection, for example, is associated with a distinctive neuropathoge nesis that includes marked cortical atrophy, cognitive disorders, and pyramidal dysfunction. The ability of HIV's envelope glycoprotein, gp1 20, to produce increased intracellular free calcium ([Ca2+](i)) leadin g to neuronal death has been documented. We hypothesize that gp120 and the envelope glycoproteins of other retroviruses may have similar cal cium-increasing effects in advancing growth cones, a property which co uld disrupt the orderly development of the nervous system. To explore this possibility, we exposed chick ciliary ganglion neurons in culture to a known cytopathic region (CVR5) of the feline leukemia virus' env elope glycoprotein. CVR5 produced [Ca2+](i) increases and dose-depende nt morphological changes in growth cones isolated from their cell bodi es by axotomy. These responses of growth cones to CVR5 suggest that th e neurotoxic effects of retroviruses could be mediated at the level of the individual growth cone through exposure to envelope glycoproteins and could constitute one mechanism by which these viruses perturb the normal development of the nervous system.