Abstract: Disclosed are methods for conditionally immortalizing stem cells, including adult and embryonic stem cells, the cells produced by such methods, therapeutic and laboratory or research methods of using such cells, and methods to identify compounds related to cell differentiation and development or to treat diseases, using such cells. A mouse model of acute myeloid leukemia (AML) and cells and methods related to such mouse model are also described.

Abstract: Pharmaceutical compositions comprising the HIV protein vpr or nucleic acid molecule encoding vpr are disclosed. Also disclosed are methods of treating patients suffering from diseases characterized by hyperproliferating undifferentiated cells such as cancer by administering such compositions. Methods of identifying compounds which have anti-HIV activity are disclosed, in particular, methods of identifying compounds which modulate the activity of vpr and of identifying compounds which inhibit vpr binding to the HIV protein gag.

Abstract: Method of inhibiting proliferation of cells using vpr protein or nucleotide sequences that encode vpr are disclosed. Method of preventing lymphocyte activation using vpr protein or nucleotide sequences that encode vpr are disclosed. Methods of treating an individual diagnosed with or suspected of suffering from autoimmune disease, diseases characterized by proliferating cells and graft versus host disease by administering vpr protein or a functional fragment thereof, or a nucleic acid molecule that comprises a nucleotide sequence that encodes vpr protein or a functional fragment thereof are disclosed. Conjugated compositions for delivery of active agents to the nucleus of cells are disclosed.

Abstract: Method of inhibiting proliferation of cells using vpr protein or nucleotide sequences that encode vpr are disclosed. Method of preventing lymphocyte activation using vpr protein or nucleotide sequences that encode vpr are disclosed. Methods of treating an individual diagnosed with or suspected of suffering from autoimmune disease, diseases characterized by proliferating cells and graft versus host disease by administering vpr protein or a functional fragment thereof, or a nucleic acid molecule that comprises a nucleotide sequence that encodes vpr protein or a functional fragment thereof are disclosed. Conjugated compositions for delivery of active agents to the nucleus of cells are disclosed.

Abstract: Pharmaceutical compositions comprising the HIV protein vpr or nucleic acid molecule encoding vpr are disclosed. Also disclosed are methods of treating patients suffering from diseases characterized by hyperproliferating undifferentiated cells such as cancer by administering such compositions. Methods of identifying compounds which have anti-HIV activity are disclosed, in particular, methods of identifying compounds which modulate the activity of vpr and of identifying compounds which inhibit vpr binding to the HIV protein gag.

Abstract: A method for treating an individual exposed to or infected with HIV is disclosed which comprises administering to said individual a therapeutically effective amount of one or more compounds which inhibit or prevent replication of said HIV by interfering with the replicative or other essential functions of Vpr expressed by said HIV, by interactively blocking the Vpr target in human cells, and thereby preventing translocation of the Vpr/target complex from the cytosol of said human cells to the nuclei of said cells, where Vpr carries on activities essential to replication of HIV. In preferred embodiments, the compound or compounds which interactively block the target are steroid hormone receptor antagonists, glucocorticoid receptor antagonists, or glucocorticoid receptor Type II antagonists, especially mifepristone (RU-486). Pharmaceutical compositions comprising these compounds, as well as a method for identifying them and a kit for use therein, are also disclosed.

Abstract: A human receptor protein which binds to the human immunodeficiency virus (HIV) viral protein R (vpr) is disclosed. Pharmaceutical compositions that comprise the receptor protein, compositions useful to produce the receptor protein and methods of making and using the receptor protein are disclosed.

Abstract: Human immunodeficiency virus (HIV)-1, HIV-2, and simian immunodeficiency virus contain, in addition to the canonical gag/pol/env genes, additional small open reading frames encoding gene products, including the 96-amino acid 15-kDa virion associated HIV-1 Vpr gene product. The conservation of the vpr open reading frame in primate lentiviruses suggests that vpr is critical to viral replication. A biologically active recombinant HIV-1 Vpr protein was employed as a ligand to identify its cellular targets. A novel 41-kDa cytosolic protein was identified and termed the viral protein R interacting protein, or Rip-1. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Vpr protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor (GR)-II-stimulating steroids. Vpr and Rip-1 coimmunoprecipitated with the human GR as part of a receptor complex.

Abstract: Human and simian immunodeficiency viruses (HIV/SIVs) contain, in addition to the canonical gag/pol/env genes, additional small open reading frames (ORFs) encoding gene products, including the 96-amino acid 15-kDa virion-associated HIV-1 Vpr gene product. Vpr functions as a regulator of cellular processes related to HIV replication. A biologically active recombinant HIV-1 Vpr protein was employed as a ligand to identify its cognate cellular target(s). A novel 41-kDa cytosolic viral protein R interacting protein, designated Rip-1, was identified using the recited assay. Rip-1 displays a wide-tissue distribution, including relevant targets of HIV infection. HIV-1 Vpr induced nuclear translocation of Rip-1. This invention provides novel biochemical reagents and methods that will facilitate the identification of antiviral agents.