Abstract: A method for identifying host genes and encoded proteins for potential targets for therapeutic intervention employs a Gene Search Vector that is either lentivirus or MMLV-based, and can be used to interrogate an entire cell genome without prior knowledge of the genomic sequence. This Random Homozygous Gene Perturbation (RUGP) technique is rapidly verifiable and is used to identify potential host targets for intervention for influenza, HIV and other viral infections. Using Thermal Assymetric Interlaced (TAIL)-PCR, the period for identification of promising targets is reduced from months to weeks or less. Specific targets including PTCH1, Robo1 and Nedd4 are reviewed in detail.

Abstract: The invention involves the detection of virally infected cells by antibodies or antibody fragments which selectively bind to TSG101. TSG101 is on the surface of mammalian cells, and thus available for detection by antibodies, during viral budding—a phenomenon wherein viral particles escape a virally infected cell after propagation in that cell, so as to infect other cells. To achieve budding, a protein, TSG101 is “hijacked” and misdirected to, or mis-expressed on, the surface of the infected cell. Antibodies can be used to selectively detect such infected cells. Certain TSG101 antibodies may provide therapeutic benefit when administered to infected mammals.

Abstract: The invention reflects enhanced antibody expression of an antibody of interest by cell lines transformed by random homozygous gene perturbation methods to either increase or decrease the expression pattern of a gene of the cell line other than the antibody of interest. The transformed cell line exhibits specific productivity rates, SPR, for the RHGP transformed cell liens of 1.5 or more, as compared with the antibody expressing cell line parents prior to transformation by RHGP. A knock out or anti-sense construct may be devised to reduce expression of the target gene, a promoter may be inserter to enhance expression of the target gene. The antibodies expressed by the transformed cell lines exhibit the binding properties of their parent cell lines prior to transformation with RHGP, and increase Total Volumetric Production of said antibody by said cells in a given volume.

Abstract: A method of inhibiting viral respiratory infection in a mammal in need of same, includes administering an effective amount of 2-[2-(5-carbamimidoyl-benzofuran-2-yl)-vinyl]-H-benzoimidazole-5-carboxamidine or the Bis-N-hydroxyamidine prodrug thereof, prior to viral infection, or therapeutically following viral infection, to inhibit that viral infection. The compound selectively inhibits Caspase 2 and/or 8 as to prevent infective viral particle release. It is optionally administered IV, IP, orally or via other conventional administration routes in a dosage range of 1 ng/kg-200 mg/kg of body weight.

Abstract: Compounds, pharmaceutical compositions and methods of inhibiting viral infection in a mammal in need of same, are provided, which employ compounds of the formula wherein each X is independently H or an electrodonating group, each Y is independently H, alkyl of 1-4 carbon atoms, hydroxy, alkoxy or methylene and wherein Substituent Z is a di-or-tri akly amino, or alkyl di or tri amino, optionally substituted with a halogen moiety. This family of compounds, designated FGI-104 herein, inhibits viral infection therapeutically and prophylactically.

Abstract: The present invention provides methods of using antibodies that bind a TSG101 protein to inhibit or reduce viral production. The invention also provides methods of using the TSG101 antibodies for the treatment of viral infections, including HIV infection. The invention further provides methods of detecting viral infected cells using TSG101 antibodies.

Abstract: The invention provides for inhibition of viral disease by the provision to a mammalian host of antibodies directed against an escort protein like Tsg101. These proteins appear on the surface of a cell, and thus can be bound by circulating antibodies thereto. By binding escort proteins on the cell surface, budding of viral particles is inhibited. The virus infects the initial cells, but cannot escape that cell to infect the body en masse.

Abstract: The importance of interaction between TSG101 and Vps28 in the release of HIV-1 and other viruses is disclosed. Suppressing or interfering in this interaction may inhibit HIV-1 virion release from infected cells. Agents that modulate this interaction include antibodies that bind to Vps28, polypeptides that bind to Vps28, and nucleic acids that may be used in gene therapy to interfere with the expression of wild type Vps28. Administration of such agents in vitro for screening and diagnostic purposes, and in vivo for diagnostic and therapeutic purposes, is disclosed.

Abstract: XMRV appears to be related to both prostate cancer if it infects a male germ cell and chronic fatigue syndrome in both sexes. (If the virus does not infect a germ cell). Prostate cancer cells exhibit TSG101 on the surface only upon infection with a virus like XMRV. Antibodies to TSG101 can be effective diagnostics to identify individuals with a predisposition to prostate. They can also be used in place of current diagnostics to confirm the presence of prostate cancer. TSG101 antibodies, when administered in vivo, exhibit the ability to reduce tumor size, suppress metastatic transformation and extend survival.

Abstract: The invention provides for inhibition of viral disease by the provision to a mammalian host of antibodies directed against an escort protein likeTsg 101. These proteins appear on the surface of a cell, and thus can be bound by circulating antibodies thereto. By binding escort proteins on the cell surface, budding of viral particles is inhibited. The virus infects the initial cells, but cannot escape that cell to infect the body en masse.

Abstract: Caspace inhibition provides inhibition of viral infection across a wide collection of caspaces and viruses. Caspace inhibition, the prevention of the formation of active caspaces, can be achieved either through gene therapy, protein binding an inhibition, or through small molecule administration. Examples for small molecule inhibition allow the formation of a pharmacaphore to identify more and more active small molecules.

Abstract: The invention reflects enhanced antibody expression of an antibody of interest by cell lines transformed by random homozygous gene perturbation methods to either increase or decrease the expression pattern of a gene of the cell line other than the antibody of interest. The transformed cell line exhibits specific productivity rates, SPR, for the RHGP transformed cell liens of 1.5 or more, as compared with the antibody expressing cell line parents prior to transformation by RHGP. A knock out or anti-sense construct may be devised to reduce expression of the target gene, a promoter may be inserter to enhance expression of the target gene. The antibodies expressed by the transformed cell lines exhibit the binding properties of their parent cell lines prior to transformation with RHGP, and increase Total Volumetric Production of said antibody by said cells in a given volume.

Abstract: A human gene, fg01, on chromosome 8, is identified. This gene, and its expression product, human fg01, shares a homology under 70% with the corresponding murine gene, which has been linked to presentation of the Alzheimer's phenotype of A? plaques and hyperphosphorylated tau tangles. Upregulation appears to suppress the Alzheimer's phenotype, which may be effective in preventing the onset of symptoms or progression of symptoms associated with AD. Screening methods are also set forth.

Abstract: A human gene, fg01, on chromosome 8, is identified, as well as a truncated form on chromosome 5. Upregulation appears to suppress the Alzheimer's phenotype, (AB plaques and hyperphosphorylated tau tangles) which may address the onset of symptoms or progression of symptoms associated with AD. Screening methods are also set forth.

Abstract: A method for identifying host genes and encoded proteins for potential targets for therapeutic intervention employs a Gene Search Vector that is either lentivirus or MMLV-based, and can be used to interrogate an entire cell genome without prior knowledge of the genomic sequence. This Random Homozygous Gene Perturbation (RUGP) technique is rapidly verifiable and is used to identify potential host targets for intervention for influenza, HIV and other viral infections. Using Thermal Assymetric Interlaced (TAIL)-PCR, the period for identification of promising targets is reduced from months to weeks or less. Specific targets including PTCH1, Robo1 and Nedd4 are reviewed in detail.

Abstract: The invention reflects enhanced antibody expression of an antibody of interest by cell lines transformed by random homozygous gene perturbation methods to either increase or decrease the expression pattern of a gene of the cell line other than the antibody of interest. The transformed cell line exhibits specific productivity rates, SPR, for the RHGP transformed cell liens of 1.5 or more, as compared with the antibody expressing cell line parents prior to transformation by RHGP. A knock out or anti-sense construct may be devised to reduce expression of the target gene, a promoter may be inserter to enhance expression of the target gene. The antibodies expressed by the transformed cell lines exhibit the binding properties of their parent cell lines prior to transformation with RHGP, and increase Total Volumetric Production of said antibody by said cells in a given volume.

Abstract: Compounds that possess anti-infective activity are described. Methods of using these compounds for the treatment or prevention of infectious diseases such as acquired immunodeficiency syndrome (AIDS) are also described. The compounds inhibit HIV infectivity and do not exhibit significant cytotoxicity in HIV producing cells.

Abstract: Genes relating to resistance to infection by influenza virus are identified. The genes and the gene products (i.e., the polynucleotides transcribed from and polypeptides encoded by the genes) can be used for the prevention and treatment of influenza. The genes and the gene products can also be used to screen agents that modulate the gene expression or the activities of the gene products.

Abstract: The invention involves the detection of virally infected cells by antibodies or antibody fragments which selectively bind to TSG101. TSG101 is on the surface of mammalian cells, and thus available for detection by antibodies, during viral budding—a phenomenon wherein viral particles escape a virally infected cell after propagation in that cell, so as to infect other cells. To achieve budding, a protein, TSG101 is “hijacked” and misdirected to, or mis-expressed on, the surface of the infected cell. Antibodies can be used to selectively detect such infected cells. Certain TSG101 antibodies may provide therapeutic benefit when administered to infected mammals.

Abstract: The present invention provides antibodies that bind to the C-terminal region of TSG101. The invention also provides methods of using the TSG101 antibodies for the treatment of viral infections, including HIV and Ebola virus infection.