| 摘要 |
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 alpha4 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 alpha4 gene, has a secondary mutation in the gene Us3 specifying a protein kinase. Thus a functional Us3, 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 Us3 or an Us3 encoding gene, methods of inhibiting Us3's apoptosis-inhibiting function and methods for the production of recombinant proteins and treatment of HSV infections. |
