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