Abstract
Neuropathogenic processes that affect the pathfinding properties of neuronal 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 neuropathogenesis that includes marked cortical atrophy, cognitive disorders, and pyramidal dysfunction. The ability of HIV's envelope glycoprotein, gp120, to produce increased intracellular free calcium ([Ca2+]i) leading to neuronal death has been documented. We hypothesize that gp120 and the envelope glycoproteins of other retroviruses may have similar calcium-increasing effects in advancing growth cones, a property which could 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’ envelope glycoprotein. CVR5 produced [Ca2+]i increases and dose-dependent morphological changes in growth cones isolated from their cell bodies by axotomy. These responses of growth cones to CVR5 suggest that the 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.