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Demonstration of scrapie strain diversity in infected PC12 cells
R Rubenstein1, H Deng, R E Race
1Department of Virology, Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314.
Abstract:
Scrapie strain replication in the nerve growth factor-induced, differentiated PC12 cell culture system was examined. Differences in replication between mouse-derived agents were demonstrated, with the 139A scrapie strain yielding 100- to 1000-fold higher levels of infectivity than the ME7 scrapie strain. Replication was not detected in PC12 cells infected with either the hamster-derived 263K or rat-derived 139R scrapie strains. Studies on the neurotransmitters in infected PC12 cells demonstrated that the adrenergic pathway was unchanged but the cholinergic pathway was altered. Furthermore, the degree of alteration correlated with the level of scrapie strain replication. Comparison of infectivity titres and enzymatic changes in ME7-infected PC12 cells with those in Chandler agent-infected mouse neuroblastoma cells suggests that the significant changes in neurotransmitter levels in cultures exhibiting low titres of infectivity involve factors in addition to strain replication. The variation in the range of scrapie strain replication in PC12 cells is discussed in relationship to species barrier, cell targeting, genetic susceptibility and species strain specificity. These studies further emphasize the value of the PC12 cell model system in examining the scrapie strain-host cell interaction and in addition support the concept of variation among scrapie strains.
Insights
Scrapie strains show varied replication in PC12 cells, impacting neurotransmitter levels. This highlights strain-specific interactions and the PC12 cell model
Area of Science:
- Neuroscience
- Cell Biology
- Prion Disease Research
Background:
- Scrapie is a prion disease affecting the central nervous system.
- Understanding scrapie strain-host interactions is crucial for disease research.
- PC12 cell cultures offer a model for studying neuronal responses to infection.
Purpose of the Study:
- To investigate the replication of different scrapie strains in differentiated PC12 cells.
- To analyze the impact of scrapie infection on neurotransmitter pathways in PC12 cells.
- To explore factors influencing scrapie strain variability in cell culture models.
Main Methods:
- Infection of nerve growth factor-induced PC12 cells with various mouse, hamster, and rat-derived scrapie strains.
- Quantification of scrapie infectivity titers using cell culture assays.
- Measurement of neurotransmitter levels (adrenergic and cholinergic pathways) in infected PC12 cells.
Main Results:
- Mouse-derived 139A scrapie strain showed significantly higher replication (100-1000 fold) than the ME7 strain in PC12 cells.
- No detectable replication of hamster (263K) or rat (139R) scrapie strains was observed.
- Cholinergic pathways were altered in infected PC12 cells, with changes correlating to scrapie replication levels; adrenergic pathways remained unchanged.
Conclusions:
- PC12 cell cultures demonstrate differential susceptibility to various scrapie strains, indicating strain-specific host-cell interactions.
- Scrapie replication influences cholinergic neurotransmission in PC12 cells, suggesting a link between prion activity and neuronal function.
- The PC12 cell model is valuable for studying scrapie strain diversity and host-pathogen interactions, supporting the concept of scrapie strain variation.