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 system disease. Our objective was to characterize the neurotoxicity of a peptide sequence derived from an animal retrovirus, the feline leukemia virus (FeLV). Using a peptide sequence from the subtype FeLV-C envelope protein variable region 5 (VR5), cytotoxicity was demonstrated in studies that evaluated neuronal survival, neurite outgrowth, and alterations in intracellular calcium ion concentration. The FeLV subtype isolate FeLV-CSarma possesses an envelope protein VR5 amino acid sequence that varies by four amino acids from the VR5 amino acid sequence of subtype FeLV-AGlasgow. The polypeptide representing the VR5 of FeLV-CSarma (FeLV-CVR5) is significantly more neurotoxic than the polypeptide sequence representing the VR5 of FeLV-AGlasgow (FeLV-AVR5). FeLV-CVR5 (> or = 3 microM) exposure resulted in significant dose-dependent neurotoxicity. Antibodies to FeLV-CVR5 blocked this effect. Neurite outgrowth was significantly reduced at all tested concentrations (3-12 microM) of FeLV-CVR5, with a 92% reduction in neurite length at 12 microM. FeLV-AVR5 was significantly less neurotoxic with respect to neurite outgrowth than was FeLV-CVR5. The significant reduction in neurotoxicity for FeLV-AVR5 illustrates the importance of the 4-amino-acid difference between it and FeLV-CVR5. Alterations in intracellular calcium ion concentration were associated with this neurotoxicity.
Mitchell
T W
TW
Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
Rojko
J L
JL
Hartke
J R
JR
Mihajlov
A R
AR
Kasameyer
G A
GA
Gasper
P W
PW
Whalen
L R
LR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D005726:Ganglia, Parasympathetic / Q000166:cytology; D006706:Homeostasis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009802:Oculomotor Nerve / Q000166:cytology; D010455:Peptides / Q000494:pharmacology / Q000633:toxicity; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D010455:Peptides; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C073723:glycoprotein gp70, Feline leukemia virus; D002118:Calcium