Octapeptide repeat region of prion protein (PrP) is required at an early stage for production of abnormal prion protein in PrP-deficient neuronal cell line

An abnormal isoform of prion protein (PrP Sc ), which is composed of the same amino acids as cellular PrP (PrP C ) and has proteinase K (PK)-resistance, hypothetically converts PrP C into PrP Sc . To investigate the region important for PrP Sc production, we examined the levels of PrP Sc in PrP gene-deficient cells (HpL3-4) expressing PrP C deleted of various regions including the octapeptide repeat region (OR) or hydrophobic region (HR). After Chandler or Obihiro prion infection, PrP Sc was produced in HpL3-4 cells expressing wild-type PrP C or PrP C deleted of HR at an early stage and further reduced to below the detectable level, whereas cells expressing PrP C deleted of OR showed no PrP Sc production. The results suggest that OR of PrP C is required for the early step of efficient PrP Sc production.