Abstract: The present invention concerns methods of compositions for inhibiting or inducing apoptosis in a cell. The methods and compositions concern either the herpesviral protein US3, the cellular pro-apoptotic polypeptide BAD, or modulators thereof to modulate apoptosis in a cell.

Abstract: The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an a4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

Abstract: The present invention provides methods of expressing a nucleic acid or producing a proteinaceous composition encoded by a nucleic acid in vascular and cardiovascular cells by administration of a herpesvirus vector. The present invention provides methods of producing a therapeutic benefit in vascular and cardiovascular tissue by administration of a herpesvirus vector. In additional aspects, the invention concerns combination therapies for vascular and cardiovascular diseases comprising administration of a herpesvirus vector and treatment with at least one addition pharmacological agent or surgical procedure.

Abstract: The present invention relates to the identification and purification of a herpes protease and a nucleic acid segment coding for two proteins. The first protein is the herpes protease which is able to cleave itself and also cleave the second protein. This protease is required for the assembly of the herpes virus capsid, therefore is essential for replication. The second protein has previously been designated as the family of proteins in viral infected cells, ICP35. The protease and its substrates are encoded by overlapping nucleic acid segments. This invention also relates to a promoter sequence for the second protein. Methods are presented of producing a viral protease, screening a protease inhibitor which may be used in a drug designed for the treatment of herpes disease, methods for treating herpes and other viral infections wherein the virus employs a protease substantially similar to the herpes protease, for capsid production.

Abstract: The present invention is directed to methods and compositions relating to the treatment of herpes simplex virus infections and the screening of compounds for activity that inhibit or promote viral latency. The previously identified ORF P gene product now has been shown to interact with certain eukaryotic splicing factors and, in a cell infected with a herpesvirus containing a derepressed ORF P gene, ORF P can limit the splicing of at least two viral products. Given this function, it now is possible to screen for inhibitors and inducers of ORF P and, further, provide methods for maintaining and preventing viral latency.

Abstract: Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus.

Abstract: The present invention provides the gene product of the herpes simplex virus UL13 gene as being capable of phosphorylating other gene products of the herpes simplex virus. The herpes simplex virus UL13 gene product is used in an assay to identify substances suspected of having anti-herpes simplex viral activity.

Abstract: The present invention relates to methods of treatment of programmed cell death (apoptosis) through the use of the HSV-1 gene &ggr;134.5 or the product of its expression, ICP34.5. The gene and its expression have been demonstrated to be required for HSV-1 neurovirulence, and in particular, to act as an inhibitor of neuronal programmed cell death which allows for viral replication. Use of the gene therapy, or the protein itself, can be expected to result in inhibition of programmed cell death in various neurodegenerative diseases. This invention also relates to novel vectors for gene therapy, including modified herpes virus. Methods are presented for conducting assays for substances capable of mimicing, potentiating or inhibiting the expression of &ggr;134.5 or the activity of ICP34.5. Also, methods are disclosed for the treatment of tumorogenic diseases, including cancer, and for treatment of herpes and other viral infections using inhibitors of &ggr;134.5 expression or ICP34.5 activity.

Abstract: The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an &agr;4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections. Further, the present invention discloses that the HSV-1 mutant lacking the &agr;4 gene, has a secondary mutation in the gene Us3 specifying a protein kinase.

Abstract: The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an &agr;4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

Abstract: The present invention relates to methods of treatment of programmed cell death (apoptosis) through the use of the HSV-1 gene &ggr;134.5 or the product of its expression, ICP34.5. The gene and its expression have been demonstrated to be.required for HSV-1 neurovirulence, and in particular, to act as an inhibitor of neuronal programmed cell death which allows for viral replication. Use of the gene therapy, or the protein itself, can be expected to result in inhibition of programmed cell death in various neurodegenerative diseases. This invention also relates to novel vectors for gene therapy, including modified herpes virus. Methods are presented for conducting assays for substances capable of mimicing, potentiating or inhibiting the expression of &ggr;134.5 or the activity of ICP34.5. Also, methods are disclosed for the treatment of tumorogenic diseases, including cancer, and for treatment of herpes and other viral infections using inhibitors of &ggr;134.5 expression or ICP34.5 activity.

Abstract: A recombinant herpes simplex virus genome having modified .gamma..sub.1 34.5 genes incapable of expressing an active ICP34.5 gene product, vaccines comprising the recombinant herpes simplex virus genome methods for immunizing a host against the herpes simplex virus using the recombinant herpes simplex virus genome, and a method for preparing the vaccine are disclosed.

Abstract: A foreign gene is inserted into a viral genome under the control of promoter-regulatory regions of the genome, thus providing a vector for the expression of the foreign gene. DNA constructs, plasmid vectors containing the constructs useful for expression of the foreign gene, recombinant viruses produced With the vector, and associated methods are disclosed.

Abstract: A live, attenuated HSV-2 virus and methods of making and using the virus are provided. The live, attenuated HSV-2 virus is constructed using recombinant techniques and can be used in a pharmaceutical composition for prophylactic treatment of HSV-2 infections and for treatment of recurrent HSV-2 related diseases and conditions. Additionally, a plasmid vector is disclosed for expressing a GST-UL56 fusion protein wherein the protein comprises the Glutathione S Transferase gene product fused to at least an immunogenic portion of the HSV-2 UL56 gene product. The GST-UL56 fusion protein can be used to produce polyclonal antisera to the HSV-2 UL56 gene product, to detect whether recombinant HSV-2 deletion mutants express UL56, and as a type-specific reagent capable of discerning HSV-1 from HSV-2.

Abstract: The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an .alpha.4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

Abstract: A foreign gene is inserted into a viral genome under the control of promoter-regulatory regions of the genome, thus providing a vector for the expression of the foreign gene. DNA constructs, plasmid vectors containing the constructs useful for expression of the foreign gene, recombinant viruses produced with the vector, and associated methods are disclosed.

Abstract: The present invention is directed to methods and compositions relating to the treatment of herpes simplex virus infections and the screening of compounds for activity that inhibit or promoter viral latency. The previously identified ORF P gene product now has been shown to interact with certain eukaryotic splicing factors and, in a cell infected with a herpesvirus containing a derepressed ORF P gene, ORF P can limit the splicing of at least two viral products. Given this function, it now is possible to screen for inhibitors and inducers of ORF P and, further, provide methods for maintaining and preventing viral latency.

Abstract: Methods for the identification of inducers and inhibitors of apoptosis are described. The method exploits the finding that the exposure of cells to apoptotic stress and its concurrent shutdown of cellular protein synthesis is accompanied by phosphorylation of IF-2.alpha. and a novel protein termed p90.

Abstract: Methods for identifying inducers and inhibitors of programmed cell death in a cell-free system are described. The methods exploit the finding that programmed cell death is accompanied by shutdown of cellular protein synthesis and by phosphorylation of eIF-2.alpha. and that the dephosphorylation of eIF-2.alpha. prevents the shutdown of protein synthesis.

Abstract: The present invention relates to synthetic herpes simplex virus (HSV) promoters which are constructed by operatively linking the 5' nontranscribed domain of an HSV .alpha. gene to a fragment containing the transcription initiation site and the 5' transcribed noncoding region from an HSV .gamma. gene. Synthetic promoters of the invention that are operatively linked to heterologous genes, inserted into HSV genomes and used to generate live virus are useful for expressing polypeptides encoded by the heterologous genes in appropriate host cells. The synthetic promoters direct transcription of the heterologous genes constitutively throughout the reproductive cycle of the virus at a high cumulative level. The recombinant viruses of the invention can also be used as vaccines to present polypeptides against which a host will mount an immune response.