Arch Development Corporation

Rosario Leopardi

Bernard Roizman

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.

Herpes simplex virus ICP4 is an inhibitor of apoptosis

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 U,3 specifying a protein kinase. Thus a functional U,3, a viral gene encoding a protein kinase known to phosphorylate serine/theonine within a specific arginine rich consensus sequence, is required in order to block apoptosis. Also disclosed are methods for inhibition of apoptosis using U,3 or an U,3 encoding gene, methods of inhibiting U,3's apoptosis-inhibiting function and methods for the production of recombinant proteins and treatment of HSV infections.

Herpes simplex virus US3 and ICP4 as inhibitors of apoptosis

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.

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Chicago, IL, United States of America

Rosario Leopardi