Abstract: The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR?/?, STAT1?/? or both PKR?/? and STAT1?/?. The virus is selected from the group consisting of Rhabdovirus and picornavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

Abstract: The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR?/?, STAT1?/? or both PKR?/? and STAT1?/?. The virus is selected from the group consisting of Rhabdovirus and picomavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

Abstract: The present invention relates to hepatitis C virus (HCV). More particularly, the invention relates to the development of a tool suitable for the search, discovery and validation of novel HCV antiviral drugs and therapies (e.g. vaccine). The invention further relates to methods for inducing HCV replication in vitro, and more particularly to a simple in vitro replication assay for HCV. In addition, the invention relates to the use of the methods of the present invention to prognose the resistance/sensitivity of a particular strain of HCV to a chosen anti-HCV agent. In one embodiment, the present invention relates to an adaptation of a therapeutic regimen for a patient infected with HCV which takes into account the resistance/sensitivity phenotype of the HCV strain which infects same.

Abstract: The present invention relates to hepatitis C virus (HCV). More particularly, the invention relates to the development of a tool suitable for the search, discovery and validation of novel HCV antiviral drugs and therapies (e.g. vaccine). The invention further relates to methods for inducing HCV replication in vitro, and more particularly to a simple in vitro replication assay of HCV which enables productive and sustained infectious HCV production.

Abstract: The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR−/−, STAT1−/− or both PKR−/− and STAT1−/−. The virus is selected from the group consisting of Rhabdovirus and picomavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

Abstract: The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR−/−, STAT1−/− or both PKR−/− and STAT1−/−. The virus is selected from the group consisting of Rhabdovirus and picornavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

Abstract: Viral gene constructs and modified viruses contain properties which permit them to replicate or have activity only in target cells such as diseased or otherwise infected cells.

Abstract: More than 30% of human malignancies harbor encogenic Ras. Both pro-apoptotic and anti-apoptotic pathways emanate from encogenic Ras with survival being dominant. Ras survival signaling is thought to be controlled by transcriptional and post-translational processes. The present invention shows that a repressor of cap-dependent translation initiation, 4E-BP1, selectively activates apoptosis in Ras-transformed fibroblasts and eliminates Ras-induced chemoresistance. These effects of 4E-BP1 are strictly dependent on its ability to sequester translation initiation factor eIF4E, thereby preventing its assembly into an active pre-initiation complex. These results suggest that translational control is critical for prevention of apoptosis and resistance to antitumor agents in Ras-transformed cells.

Abstract: The eukaryotic mRNA 5′ cap structure is recognized by eIF4E, which plays an essential role in translational control and cell growth. Members of a family of proteins called eIF4E-binding proteins (4E-BPs) inhibit the activity of eIF4E and consequently repress translation. Following exposure of cells to hormones, cytokines and growth factors, 4E-BPs become hyperphosphorylated and dissociate from eIF4E, to relieve translation inhibition. The phosphorylation events leading to 4E-BP1 dissociation from eIF4E are mediated by the P13-kinase/FRAP/mTOR signaling pathway. The present study addresses the biological importance of 4E-BP1 in vivo by disrupting its gene in the mouse. Homozygous 4E-BP1 deficient mice are healthy and develop normally. However, they show an important decrease in white adipose tissue and blood glucose level, and the males show a decrease in total body weight and an increase in resting metabolic rate.

Abstract: The present invention relates to novel human Prt1 (hPrt1) and eIF4G-like (p97) proteins which are involved in eukaryotic transcription In particular, isolated nucleic acid molecules are provided encoding the human hPrt1 and p97 proteins. hPrt1 and p97 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of hPrt1 and p97 activity. Also provided are therapeutic methods for treating disease states associated with the hPrt1 and p97 proteins.

Abstract: Method for screening for a non-hormone agent potentially useful to treat a hormone disorder The method involves contacting a potential agent with a system containing a cellular component and a translation factor. The component and factor interact with one another in an intact normal cell in a manner responsive to the hormone to cause a modulation of translation in the cell. The method involves determining whether the agent causes a modulation of translation by the component and the factor analogous to that which occurs in intact cells in response to the hormone.

Abstract: The present invention relates to novel human Prt1 (hPrt1) and eIF4G-like (p97) proteins which are involved in eukaryotic transcription In particular, isolated nucleic acid molecules are provided encoding the human hPrt1 and p97 proteins. hprt1 and p97 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of hPrt1 and p97 activity. Also provided are therapeutic methods for treating disease states associated with the hPrt1 and p97 proteins.

Abstract: The present invention relates to novel human Prt1 (hPrt1) and eIF4G-like (p97) proteins which are involved in eukaryotic transcription. In particular, isolated nucleic acid molecules are provided encoding the human hPrt1 and p97 proteins. hPrt1 and p97 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of hPrt1 and p97 activity. Also provided are therapeutic methods for treating disease states associated with the hPrt1 and p97 proteins.

Abstract: Method for screening for a non-hormone agent potentially useful to treat a hormone disorder The method involves contacting a potential agent with a system containing a cellular component and a translation factor. The component and factor interact with one another in an intact normal cell in a manner responsive to the hormone to cause a modulation of translation in the cell. The method involves determining whether the agent causes a modulation of translation by the component and the factor analogous to that which occurs in intact cells in response to the hormone.

Abstract: The present invention relates to novel human Prt1 (hPrt1) and eIF4G-like (p97) proteins which are involved in eukaryotic transcription. In particular, isolated nucleic acid molecules are provided encoding the human hPrt1 and p97 proteins. hPrt1 and p97 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of hPrt1 and p97 activity. Also provided are therapeutic methods for treating disease states associated with the hPrt1 and p97 proteins.

Abstract: A detailed three-dimensional structure for the least abundant of the general translation initiation factors in eukaryotes, eIF4E, complexed with a ligand is disclosed. The novel N-terminal truncated eIF4Es which were constructed so as to omit a significant portion of the flexible N-terminal tail of the eIF4E are also part of the present invention. In addition, the crystals of the protein-ligand complexes containing the N-terminal truncated eIF4Es are also included. Furthermore, methods of identifying antagonists of the eIF4E protein which can be used to regulate protein synthesis in cells are also disclosed.

Abstract: Method for screening for a non-hormone agent potentially useful to treat a hormone disorder. The method involves contacting a potential agent with a system containing a cellular component and a translation factor. The component and factor interact with one another in an intact normal cell in a manner responsive to the hormone to cause a modulation of translation in the cell. The method involves determining whether the agent causes a modulation of translation by the component and the factor analogous to that which occurs in intact cells in response to the hormone.

Abstract: A detailed three-dimensional structure for the least abundant of the general translation initiation factors in eukaryotes, eIF4E, complexed with a ligand is disclosed. The novel N-terminal truncated eIF4Es which were constructed so as to omit a significant portion of the flexible N-terminal tail of the eIF4E are also part of the present invention. In addition, the crystals of the protein-ligand complexes containing the N-terminal truncated eIF4Es are also included. Furthermore, methods of identifying antagonists of the eIF4E protein which can be used to regulate protein synthesis in cells are also disclosed.

Abstract: Described herein are oligopeptides useful to inhibit replication in virally infected individuals. In a preferred embodiment of the invention, the oligopeptide is a D-arginine nonamer having N- and C-terminal protecting groups, which, at a 3 uM concentration, exhibits greater than 95% inhibition of HIV replication, in a standard assay.

Abstract: A method of screening human tissue for the presence of neoplastic cells, by determining the activity of PKR, P58 of anti-P58 in test cells being screened, and identifying candidate neoplastic cells on the basis of subnormal PKR, P58, or anti-P58 activity. The activities may be determined directly by measuring protein kinase activity or its equivalent, or measured indirectly, by detecting functional mutations in the various proteins. Also disclosed are assay kits for carrying out the screening method.