HIV-1 VPR INTERACTS WITH THE NUCLEAR TRANSPORT PATHWAY TO PROMOTE MACROPHAGE INFECTION

HIV-1 Vpr promotes nuclear entry of viral nucleic acids in nondividing macrophages and also causes a G(2) cell-cycle arrest. Consistent with its role in nuclear transport, we show Vpr localizes to the nuclear e nvelope in both human and yeast cells. Like the importin-beta subunit of the nuclear import receptor, Vpr also interacts with the yeast impo rtin-alpha subunit and nucleoporins. Moreover, overexpression of eithe r Vpr or importin-beta in yeast blocks nuclear transport of mRNAs. A m utant form of Vpr (Vpr F34I) that does not localize at the nuclear env elope, or bind to importin-alpha and nucleoporins, renders HIV-1 incap able of infecting macrophages efficiently. Vpr F34I, however, still ca uses a G(2) arrest, demonstrating that the dual functions of Vpr are g enetically separable. Our data suggest Vpr functionally resembles impo rtin-beta in nuclear import of the HIV-1 pre-integration complex and t his function is essential for the role of Vpr in macrophage infection, but not G(2) arrest.