The prion protein has DNA strand transfer properties similar to retroviralnucleocapsid protein

The transmissible spongiform encephalopathies are fatal neurodegenerative d iseases that are associated with the accumulation of a protease-resistant f orm of the cellular prion protein (PrP). Although PrP is highly conserved a nd widely expressed in vertebrates, its function remains a matter of specul ation. Indeed PrP null mice develop normally and are healthy. Recent result s show that PrP binds to nucleic acids in vitro and is found associated wit h retroviral particles. Furthermore, in mice the scrapie infectious process appears to be accelerated by MuLV replication. These observations prompted us to further investigate the interaction between PrP and nucleic acids, a nd compare it with that of the retroviral nucleocapsid protein (NC). As the major nucleic acid-binding protein of the retroviral particle, NC protein is tightly associated with the genomic RNA in the virion nucleocapsid, wher e it chaperones proviral DNA synthesis by reverse transcriptase. Our result s show that the human prion protein (huPrP) functionally resembles NCp7 of HIV-1. Both proteins form large nucleoprotein complexes upon binding to DNA . They accelerate the hybridization of complementary DNA strands and chaper one viral DNA synthesis during the minus and plus DNA strand tranfers neces sary to generate the long terminal repeats. The DNA-binding and strand tran sfer properties of huPrP appear to map to the N-terminal fragment comprisin g residues 23 to 144, whereas the C-terminal domain is inactive. These find ings suggest that PrP could be involved in nucleic acid metabolism in vivo. (C) 2001 Academic Press.