DIFFERENTIAL ASSOCIATION OF URACIL DNA GLYCOSYLASE WITH SIVSM VPR ANDVPX PROTEINS

The HIV-1 Vpr protein is a virion-associated protein which has been sh own to facilitate infection of nondividing macrophages and additionall y to alter cell cycle and proliferation status of the infected host ce ll. HIV-1 Vpr also was recently shown to associate with the DNA repair enzyme uracil DNA glycosylase (UDG). This association with a DNA repa ir enzyme is intriguing given that nonprimate lentiviruses encode a dU TPase, which, like UDG, minimizes the misincorporation of uracil into DNA and is important for virus replication in primary nondividing macr ophages but not in dividing cells. This raises the possibility that th e dependence upon Vpr for infection of nondividing macrophages may rel ate to its ability to interact with UDG. Members of the HIV-2/SIVSM gr oup encode, in addition to Vpr, a related protein called Vpx. We previ ously demonstrated (Fletcher at al., 1996) that Vpx of HIV-2/SIVSM is necessary and sufficient for infection of primary macaque macrophages, while Vpr is not required for macrophage infection but governs cell c ycle arrest. Here, we extend on these observations by demonstrating th at Vpr, but not Vpx of HIV-2/SIVSM, associates with UDG, which suggest s that Vpx facilitates infection of macrophages by a UDG-independent m echanism. (C) 1998 Academic Press.