Heterologous PrP molecules interfere with accumulation of protease-resistant Prp in scrapie-infected murine neuroblastoma cells

• Published in: Journal of Virology Vol. 68; no. 8; pp. 4873 - 4878
• Main Authors: Priola, S.A, Caughey, B, Race, R.E, Chesebro, B
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01-08-1994
• Subjects: Animals; Base Sequence; Biological and medical sciences; CEREBRO; CULTIVO DE CELULAS; CULTURE DE CELLULE; DNA, Viral; ENCEPHALE; Endopeptidases - metabolism; EXPERIMENTACION IN VIVO; EXPERIMENTATION IN VIVO; Human viral diseases; INFECCION EXPERIMENTAL; INFECTION EXPERIMENTALE; Infectious diseases; Medical sciences; Methionine - metabolism; Mice; Molecular Sequence Data; MUTACION; MUTATION; Neuroblastoma; Prions - metabolism; Prions - pathogenicity; PROTEASAS; PROTEASE; PROTEINAS; PROTEINE; PROTEOLISIS; PROTEOLYSE; PrPSc Proteins; RATON; Recombinant Proteins - metabolism; SISTEMA NERVIOSO; SOURIS; SYSTEME NERVEUX; Tumor Cells, Cultured; Viral diseases; Viral diseases of the nervous system; Virus Replication; VIRUS TEMBLADERA DE LOS OVINOS; VIRUS TREMBLANTE DU MOUTON; Nervous system diseases; Scrapie; Enzyme; Molecular interaction; Cerebral disorder; Infection; Virus; Resistance; Cell line; Viral disease; Central nervous system disease; Hydrolases; Degenerative disease; Infected cell; Proteinases; Slow virus
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.68.8.4873-4878.1994

Mutations within a host cellular protein, PrP, have been associated with disease in the transmissible spongiform encephalopathies. Murine neuroblastoma cells persistently infected with mouse scrapie accumulate protease-resistant PrP (PrP-res), the abnormal form of PrP associated with disease in the transmissible spongiform encephalopathies. These cells provide a controlled system in which to study the molecular interactions which are important in the formation of PrP-res. We have expressed recombinant PrP molecules in mouse scrapie-infected murine neuroblastoma cells and assayed the effect of these heterologous Prp genes on the formation and accumulation of PrP-res. The results demonstrate that expression of heterologous PrP molecules which differ from the endogenous PrP by as little as one amino acid can profoundly interfere with the overall accumulation of PrP-res. The data suggest that precise interactions between homologous PrP molecules are important in PrP-res accumulation and that heterologous PrP molecules can block these interactions