Analysis of the interactions between HIV-1 and the cellular prion protein in a human cell line.
The cellular prion protein (PrP(c)) is highly conserved in mammals and expressed widely in different tissues but its physiological role remains elusive. Recently, the human PrP(c) 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 PrP(c) could influence HIV-1 replication. We used the human 293T cell line as a model system, since only a very low level of PrP(c) 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 PrP(c). A PrP(c) mutant lacking the glycosylphosphatidylinositol (GPI) anchor peptide did not impair HIV-1 production, suggesting that PrP(c) trafficking is critical for this inhibitory effect. Coexpressing HIV-1 and PrP(c) in these cells also caused a fraction of PrP(c) to become partially proteinase K-resistant (PrP(res)), further illustrating the interactions between HIV-1 and PrP(c).
Leblanc
Pascal
P
INSERM U412 Ecole Normale Supérieure de LYON, Lyon, France. pascal.leblanc@ens-lyon.fr
Baas
Dominique
D
Darlix
Jean-Luc
JL
D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D019286:Endopeptidase K / Q000378:metabolism; D015686:Gene Products, env / Q000378:metabolism; D016336:Gene Products, vpr / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D021962:Membrane Microdomains; D009154:Mutation; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000235:genetics; D012313:RNA / Q000096:biosynthesis; D054325:vpr Gene Products, Human Immunodeficiency Virus
D051242:Caveolin 1; D022461:Caveolins; D015686:Gene Products, env; D016336:Gene Products, vpr; D018621:PrPC Proteins; D011328:Prions; D021382:Protein Sorting Signals; D054325:vpr Gene Products, Human Immunodeficiency Virus; D012313:RNA; D019286:Endopeptidase K