NR ATFY
AU Schätzl,H.M.; Nunziante,M.; Ertmer,A.; Kehler,C.; Maas,E.; Vorberg,I.
TI New cell culture models for study of biogenesis and cellular clearance of prions
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-29
PT Konferenz-Vortrag
AB Cultured cells able to propagate prions are valuable tools for deciphering the mechanisms of prion biogenesis and clearance. We report cell culture models in which we can study the behaviour of innate immune cells towards propagation or clearance of prions. We challenged macrophage and microglia cell lines with various prion strains in the presence or absence of PAMPs (pathogen-associate molecular patterns), monitoring uptake and clearance of PrPsc. Interestingly, stimulation with PAMPs led to a transient increase of PrPsc levels compared to control cells. This feature is influenced by cell type and prion strain. This data indicates that stimulation of innate immune cells can support transient prion propagation. A possible explanation is that PrPc cell surface expression was transiently increased in stimulated cells. Systems like this help to analyse the intrinsic cellular mechanisms of prion clearance and to manipulate the balance between de novo generation and clearance. In addition, these findings are relevant to in vivo co-infection scenarios. Another avenue of research uses PrPc-deficient cells in which we have stably introduced PrP. Such cells are used for addressing the infection behaviour in relation to amino acid requirements of the PrP substrate, in the absence of endogenous wild-type PrP. Finally, we have studied PrP mutants for their biochemical behaviour and convertibility into PrPsc. Focussing on N-terminal deletions we have found that 'Shmerling' PrP mutants display an aberrant metabolism in cultured cells, but can be converted into PrPsc isoforms. Our examinations back up the value of cell culture models in the study of the biogenesis and pathogenesis of prion proteins.
AD H.M.Schätzl, M.Nunziante, A.Ertmer, C.Kehler, E.Maas, I.Vorberg, Institute of Virology, Technical University of Munich, Biedersteinerstr. 29, 80802 Munich, Germany
SP englisch
PO Deutschland