BIOCHEMICAL AND PHYSICAL-PROPERTIES OF THE PRION PROTEIN FROM 2 STRAINS OF THE TRANSMISSIBLE MINK ENCEPHALOPATHY AGENT

Transmissible mink encephalopathy (TME) has been transmitted to Syrian golden hamsters, and two strains of the causative agent, HYPER (HY) and DROWSY (DY), have been identified that have different biological properties. During scrapie, a TME-like disease, an endogenous cellular protein, the prion protein (PrP(C)), is modified (to PrP(Sc)) and accumulates in the brain. PrP(Sc)) is partially resistant to proteases and is claimed to be an essential component of the infectious agent. Purification and analysis of PrP from hamsters infected with the HY and DY TME agent strains revealed differences in properties of PrP(TME) sedimentation in N-lauroylsarcosine, sensitivity to digestion with proteinase K, and migration in polyacrylamide gels. PrP(C) and HY PrP(TME) can be distinguished on the basis of their relative solubilities in detergent and protease sensitivities. PrP(TME) from DY-infected brain tissue shared solubility characteristics of PrP from both uninfected and HY-infected tissue. Limited protease digestion of PrP(TME) revealed strain-specific migration patterns upon polyacrylamide gel electrophoresis. Prolonged proteinase K treatment or N-linked deglycosylation of PrP(TME) did not eliminate such differences but demonstrated the PrP(TME) from DY-infected brain was more sensitive to protease digestion than HY PrP(TME). Antigenic mapping of PrP(TME) with antibodies raised against synthetic peptides revealed strain-specific differences in immunoreactivity in a region of the amino-terminal end of PrP(TME) containing amino acid residues 89 to 103. These findings indicate that PrP(TME) from the two agent strains, although originating from the same host, differ in composition, conformation, or both. We conclude that PrP(TME) from the HY and DY strains undergo different posttranslational modifications that could explain differences in the biochemical properties of PrP(TME) from the two sources. Whether these strain-specific posttranslational events are directly responsible for the distinct biological properties of the HY and DY agent strains remains to be determined.