Differential association of uracil DNA glycosylase with SIVSM Vpr and Vpx proteins.
The HIV-1 Vpr protein is a virion-associated protein which has been shown to facilitate infection of nondividing macrophages and additionally to alter cell cycle and proliferation status of the infected host cell. HIV-1 Vpr also was recently shown to associate with the DNA repair enzyme uracil DNA glycosylase (UDG). This association with a DNA repair enzyme is intriguing given that nonprimate lentiviruses encode a dUTPase, which, like UDG, minimizes the misincorporation of uracil into DNA and is important for virus replication in primary nondividing macrophages but not in dividing cells. This raises the possibility that the dependence upon Vpr for infection of nondividing macrophages may relate to its ability to interact with UDG. Members of the HIV-2/SIVSM group encode, in addition to Vpr, a related protein called Vpx. We previously demonstrated (Fletcher et 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 cycle arrest. Here, we extend on these observations by demonstrating that Vpr, but not Vpx of HIV-2/SIVSM, associates with UDG, which suggests that Vpx facilitates infection of macrophages by a UDG-independent mechanism.
Sleigh
R
R
Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605, USA.
Sharkey
M
M
Newman
M A
MA
Hahn
B
B
Stevenson
M
M
D000818:Animals; D045647:DNA Glycosylases; D004260:DNA Repair; D015967:Gene Expression Regulation, Viral; D016336:Gene Products, vpr / Q000235:genetics* / Q000378:metabolism*; D016334:Genes, vpr; D015498:HIV-2 / Q000502:physiology*; D008251:Macaca; D008264:Macrophages / Q000821:virology*; D009699:N-Glycosyl Hydrolases / Q000235:genetics* / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D051981:Uracil-DNA Glycosidase; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; C074286:VPX protein, Human immunodeficiency virus 2; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase