FELV ENVELOPE PROTEIN (GP70) VARIABLE REGION-5 CAUSES ALTERATIONS IN CALCIUM HOMEOSTASIS AND TOXICITY OF NEURONS

In humans and animals, retroviruses have been implicated in nervous sy stem disease. Our objective was to characterize the neurotoxicity of a peptide sequence derived from an animal retrovirus, the feline leukem ia virus (FeLV). Using a peptide sequence from the subtype FeLV-C enve lope protein variable region 5 (VR5), cytotoxicity was demonstrated in studies that evaluated neuronal survival, neurite outgrowth, and alte rations in intracellular calcium ion concentration. The FeLV subtype i solate FeLV-C-Sarma possesses an envelope protein VR5 amino acid seque nce that varies by four amino acids from the VR5 amino acid sequence o f subtype FeLV-A(Glasgow). The polypeptide representing the VR5 of FeL V-C-Sarma (FeLV-CVR5) is significantly more neurotoxic than the polype ptide sequence representing the VR5 of FeLV-A(Glasgow) (FeLV-AVR5). Fe LV-CVR5 (greater than or equal to 3 mu M) exposure resulted in signifi cant dose-dependent neurotoxicity. Antibodies to FeLV-CVR5 blocked thi s effect. Neurite outgrowth was significantly reduced at all tested co ncentrations (3-12 mu M) Of FeLV-CVR5, with a 92% reduction in neurite length at 12 mu M. FeLV-AVR5 was significantly less neurotoxic with r espect to neurite outgrowth than was FeLV-CVR5. The significant reduct ion in neurotoxicity for FeLV-AVR5 illustrates the importance of the 4 -amino-acid difference between it and FeLV-CVR5. Alterations in intrac ellular calcium ion concentration were associated with this neurotoxic ity.