Efficient DNA transfection mediated by the C-terminal domain of human immunodeficiency virus type 1 viral protein R

Viral protein R (Vpr) of human immunodeficiency virus type I is produced la te in the virus life cycle and is assembled into the virion through binding to the Gag protein. It is known to play a significant role early in the vi ral life cycle by facilitating the nuclear import of the preintegration com plex in nondividing cells. Vpr is also able to interact with nucleic acids, and we show here that it induces condensation of plasmid DNA. We have expl ored the possibility of using these properties in DNA transfection experime nts. We report that the C-terminal half of the protein (Vpr(52-96)) mediate s DNA transfection in a variety of human and nonhuman cell lines,with effic iencies comparable to those of the best-known transfection agents. Compared with polylysine, a standard polycationic transfection reagent, Vpr(52-96) was 10- to 1,000-fold more active, Vpr(52-96)-DNA complexes were able to re ach the cell nucleus through a pH-independent mechanism. These observations possibly identify an alternate pathway for DNA transfection.