Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system
AUTOR(ES)
Brandner, Sebastian
FONTE
The National Academy of Sciences of the USA
RESUMO
Mice devoid of PrPC (Prnpo/o) are resistant to scrapie and do not allow propagation of the infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnpo/o brains but not the surrounding tissue consistently exhibits scrapie-specific pathology and allows prion replication after inoculation. Scrapie prions administered intraocularly into wild-type mice spread efficiently to the central nervous system within 16 weeks. To determine whether PrPC is required for scrapie spread, we inoculated prions intraocularly into Prnpo/o mice containing a PrP-overexpressing neurograft. Neither encephalopathy nor protease-resistant PrP (PrPSc) were detected in the grafts for up to 66 weeks. Because grafted PrP-expressing cells elicited an immune response that might have interfered with prion spread, we generated Prnpo/o mice immunotolerant to PrP and engrafted them with PrP-producing neuroectodermal tissue. Again, intraocular inoculation did not lead to disease in the PrP-producing graft. These results demonstrate that PrP is necessary for prion spread along neural pathways.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24061Documentos Relacionados
- Insight into the PrPC → PrPSc conversion from the structures of antibody-bound ovine prion scrapie-susceptibility variants
- Prion protein PrPc interacts with molecular chaperones of the Hsp60 family.
- Evidence for the role of PrPC helix 1 in the hydrophilic seeding of prion aggregates
- Efficient Lymphoreticular Prion Propagation Requires PrPc in Stromal and Hematopoietic Cells
- Overexpression of active Syrian golden hamster prion protein PrPc as a glutathione S-transferase fusion in heterologous systems.