Abstract: Provided herein are compositions and methods that allow for the study of HIV latency and reactivation. Further provided are compositions and methods for in vitro screening of agents for their ability to reactivate, suppress reactivation or inhibit transcription of HIV. Compositions for and methods for activating a cell are also provided herein. Further provided herein are methods of treating a subject using agents that reactivate latent HIV infection or agents that inhibit HIV transcription. Also provided herein are methods of activating a latent microbiological entity in a subject. Further provided herein are methods for enhancing an immune response in a subject and compositions used as a vaccination adjuvant. Methods of making disclosed cells and compositions are also provided herein.

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: 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: The present invention provides compositions and methods for targeting recombinant retroviral particles specifically to cells of interest for delivery of desired therapeutic or toxic agents. The invention provides chimeric nucleotide constructs, chimeric proteins formed of a selected viral envelope gene from which a selected sequence has been deleted and into which has been inserted all or an effective portion of a heterologous ligand, said ligand or portion thereof capable of binding to a selected receptor, recombinant viral particles formed of the chimeric proteins, a biological mediator for delivery to the target cell; and retroviral gag and pol proteins. The lack of retroviral nucleic acid renders the viral particle replication defective and non-pathogenic.

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.