Analysis of the Interactions Between HIV-1 and the Cellular Prion Protein in a Human Cell Line

The cellular prion protein (PrPc) is highly conserved in mammals and expressed widely in different tissues but its physiological role remains elusive. Recently, the human PrPc was shown to possess nucleic acid binding and chaperoning properties similar to human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein, a key viral factor in virus structure and replication. These findings prompted us to determine if PrPc could influence HIV-1 replication. We used the human 293T cell line as a model system, since only a very low level of PrPc accumulates in these cells. Expression of PrP at a high level resulted in a specific decrease of HIV-1 Env and Vpr expression. Despite similar levels of intracellular Gag, virus production was reduced by eightfold and infectivity by three- to fourfold in the presence of PrPc. A PrPc mutant lacking the glycosylphosphatidylinositol (GPI) anchor peptide did not impair HIV-1 production, suggesting that PrPc trafficking is critical for this inhibitory effect. Coexpressing HIV-1 and PrPc in these cells also caused a fraction of PrPc to become partially proteinase K-resistant (PrPres), further illustrating the interactions between HIV-1 and PrPc.