The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCp7 of HIV-1

Transmissible spongiform encephalopathies are fatal neurodegenerative disea ses associated with the accumulation of a protease-resistant form of the pr ion protein (PrP). Although PrP is conserved in vertebrates, its function r emains to be identified. In vitro PrP binds large nucleic acids causing the formation of nucleoprotein complexes resembling human immunodeficiency vir us type 1 (HIV-1) nucleocapsid-RNA complexes and in vivo MuLV replication a ccelerates the scrapie infectious process, suggesting possible interactions between retroviruses and PrP. Retroviruses, including HIV-1 encode a major nucleic acid binding protein (NC protein) found within the virus where 200 0 NC protein molecules coat the dimeric genome. NC is required in virus ass embly and infection to chaperone RNA dimerization and packaging and in prov iral DNA synthesis by reverse transcriptase (RT). In HIV-1, 5'-leader RNA/N C interactions appear to control these viral processes. This prompted us to compare and contrast the interactions of human and ovine PrP and HIV-1 NCp 7 with HIV-1 5'-leader RNA. Results show that PrP has properties characteri stic of NCp7 with respect to viral RNA dimerization and proviral DNA synthe sis by RT. The NC-like properties of huPrP map to the N-terminal region of huPrP. Interestingly, PrP localizes in the membrane and cytoplasm of PrP-ex pressing cells. These findings suggest that PrP is a multifunctional protei n possibly participating in nucleic acid metabolism.