Abstract: Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.

Abstract: Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.

Abstract: The HIV-1 protein Vif comprises a multimerization domain that allows Vif-Vif interaction and Vif multimerization, which is important for Vif function in the HIV-1 life-cycle. A method for screening for an antagonist of Vif comprises contacting the multimerization domain of Vif with a test compound that specifically binds the multimerization domain. Antagonists identified by the screening assay inhibit Vif multimerization. The antagonists inhibit essential functions of Vif and accordingly are useful as inhibitors of HIV-1 replication.

Abstract: The HIV-1 protein Vif comprises a multimerization domain that allows Vif-Vif interaction and Vif multimerization, which is important for Vif function in the HIV-1 life-cycle. A method for screening for an antagonist of Vif comprises contacting the multimerization domain of Vif with a test compound that specifically binds the multimerization domain. Antagonists identified by the screening assay inhibit Vif multimerization. The antagonists inhibit essential functions of Vif and accordingly are useful as inhibitors of HIV-1 replication.

Abstract: One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle.

Abstract: One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif, by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle.

Abstract: One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle.

Abstract: One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif, by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle.

Abstract: This invention provides recombinant, replication-competent Rhabdovirus vaccine strain-based expression vectors for expressing heterologous viral antigenic polypeptides such as immunodeficiency virus envelope proteins or subparts thereof. An additional transcription stop/start unit within the Rhabdovirus genome is inserted to express the heterologous antigenic polypeptides. The HIV-1 gp160 protein is stably and functionally expressed, as indicated by fusion of human T cell-lines after infection with the recombinant RVs. Inoculation of mice with the recombinant Rabies viruses expressing HIV-1 gp160 induces a strong humoral response directed against the HIV-1 envelope protein after a single boost with an isolated recombinant HIV-1 gp120 protein. Moreover, high neutralization titers, up to 1:800, against HIV-1 are detected in the mouse sera.

Abstract: This invention provides recombinant, replication-competent Rhabdovirus vaccine strain-based expression vectors for expressing heterologous viral antigenic polypeptides such as immunodeficiency virus envelope proteins or subparts thereof. An additional transcription stop/start unit within the Rhabdovirus genome is inserted to express the heterologous antigenic polypeptides. The HIV-1 gp160 protein is stably and functionally expressed, as indicated by fusion of human T cell-lines after infection with the recombinant RVs. Inoculation of mice with the recombinant Rabies viruses expressing HIV-1 gp160 induces a strong humoral response directed against the HIV-1 envelope protein after a single boost with an isolated recombinant HIV-1 gp120 protein. Moreover, high neutralization titers, up to 1:800, against HIV-1 are detected in the mouse sera.

Abstract: Compositions and methods for rendering a polypeptide capable of binding with Vpr and to susceptible to incorporation into a are provided. Methods of treating a human patient infected with a virus which expresses Vpr and methods of providing a polypeptide to a cell of a human patient are also included. The invention further includes a method of determining whether a polypeptide comprises a Vpr-binding region.

Abstract: Compositions and methods for rendering a polypeptide capable of binding with Vpr and to susceptible to incorporation into a are provided. Methods of treating a human patient infected with a virus which expresses Vpr and methods of providing a polypeptide to a cell of a human patient are also included. The invention further includes a method of determining whether a polypeptide comprises a Vpr-binding region.

Abstract: One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif, by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle.

Abstract: The current therapeutic approach to treating patients with HIV-1 infection involves the use of one or more highly active antiretroviral therapeutics (HAART). While efficacious, this approach does not address the existance of latently infected cells. Such latently infected cells can be reactivated, resulting in the expression of infectious virus and reinitiation of the disease process. The present invention relates to a novel and highly efficacious approach to eradication of HIV-1. Patients that are treated with HAART are then treated with an intensification regimen wherein hydroxyurea and didanosine (ddI) are given to inhibit any residual viral replication. The therapeutic regimen is continued with the addition of compounds, such as OKT3 and IL-2, that activate latently infected cells, thereby stimulating the replication of any proviruses. These re-activated viruses are subsequently inhibited by the HAART and hydroxyurea/ddI therapeutics.

Abstract: The present invention provides a method for preventing or treating a human immunodeficiency virus (HIV) infection, including a new or an asymptomatic infection as well as AIDS, comprising administering to a mammal in need thereof a HIV infection preventing or treating effective amount of a &ggr;-L-glutamnyl-L-cysteine ester compound of formula (I): wherein R is a straight chain, branched or cyclic hydrocarbon group having 1-10 carbon atoms, or a straight chain or branched hydrocarbon group having 1-5 carbon atoms substituted with an aromatic group; or the oxidized dimer obtained by dehydrogenation between two &ggr;-L-glutamyl-L-cysteine esters having formula (I).

Abstract: Methods of gene therapy, particular ribozyme-mediated gene replacement methods, are disclosed. Method of treating patients suffering from a disease associated with expression of an abnormal form of a gene, such as alpha-1 antitrypsin mutations, are disclosed. The methods comprise the steps of administering to such a patient a nucleic acid construct encoding a ribozyme and a nucleic acid construct comprising a ribozyme resistant gene encoding a wild type form of the gene product. Recombinant vectors and pharmaceutical compositions for practicing the methods are disclosed.

Abstract: A method for improving the transduction efficiency of retroviral vectors into a host cell wherein the retroviral vectors are incubated with deoxyribonucleoside triphosphates prior to transduction into the host cell is provided.

Abstract: The present invention concerns in situ polymerase chain reaction and provides methods and reagents for identifying cells containing at least one selected nucleic acid sequence which may be derived from the human immunodeficiency virus.

Abstract: The present invention concerns in situ polymerase chain reaction and provides methods and reagents for identifying cells containing at least one selected nucleic acid sequence which may be derived from the human immunodeficiency virus.