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Efficient DNA Transfection Mediated by the C-Terminal Domain of Human Immunodeficiency Virus Type 1 Viral Protein R

2000; American Society for Microbiology; Volume: 74; Issue: 12 Linguagem: Inglês

10.1128/jvi.74.12.5424-5431.2000

1098-5514

Antoine Kichler, Jean‐Christophe Pagès, Christian Leborgne, Sabine Druillennec, C. Lenoir, Dominique Coulaud, Etienne Delain, Éric Le Cam, Bernárd P. Roques, Olivier Danos,

Virus-based gene therapy research

ABSTRACT Viral protein R (Vpr) of human immunodeficiency virus type 1 is produced late 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 viral life cycle by facilitating the nuclear import of the preintegration complex 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 explored the possibility of using these properties in DNA transfection experiments. We report that the C-terminal half of the protein (Vpr 52–96 ) mediates DNA transfection in a variety of human and nonhuman cell lines with efficiencies 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 reach the cell nucleus through a pH-independent mechanism. These observations possibly identify an alternate pathway for DNA transfection.