title: FeLV envelope protein (gp70) variable region 5 causes alterations in calcium homeostasis and toxicity of neurons.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Mitchell
authors.forename: J L
authors.initials: JL
authors.lastname: Rojko
authors.forename: J R
authors.initials: JR
authors.lastname: Hartke
authors.forename: A R
authors.initials: AR
authors.lastname: Mihajlov
authors.forename: G A
authors.initials: GA
authors.lastname: Kasameyer
authors.forename: P W
authors.initials: PW
authors.lastname: Gasper
authors.forename: L R
authors.initials: LR
authors.lastname: Whalen
mesh_terms: 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
chemical_list: D010455:Peptides; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C073723:glycoprotein gp70, Feline leukemia virus; D002118:Calcium