公开(公告)号：WO9846637A3

公开(公告)日：1999-01-28

申请号：PCT/US9807573

申请日：1998-04-16

Applicant: ARCH DEV CORP ,  LEOPARDI ROSARIO ,  ROIZMAN BERNARD

Inventor： LEOPARDI ROSARIO ,  ROIZMAN BERNARD

IPC: A61K38/00 ,  C07K14/035 ,  C12N5/02 ,  C07K14/00

CPC classification number: C07K14/005 ,  A61K38/00 ,  C12N2710/16622

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 have transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an α4 gene, methods for 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 α4 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/threonine 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 for inhibiting US3's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

公开(公告)号：WO9804709A3

公开(公告)日：1998-03-12

申请号：PCT/US9712904

申请日：1997-07-23

Applicant: ARCH DEV CORP ,  LEOPARDI ROSARIO ,  ROIZMAN BERNARD

Inventor： LEOPARDI ROSSARIO ,  ROIZMAN BERNARD

IPC: C12N15/09 ,  A61K38/00 ,  A61K39/395 ,  A61K45/00 ,  A61K48/00 ,  A61P43/00 ,  C07K14/035 ,  C12N5/10 ,  C12N15/02 ,  C12N15/38 ,  C12P21/08

CPC classification number: C07K14/005 ,  A61K38/00 ,  A61K48/00 ,  C12N2710/16622

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 α4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

公开(公告)号：WO1998004709A2

公开(公告)日：1998-02-05

申请号：PCT/US1997012904

申请日：1997-07-23

Applicant: ARCH DEVELOPMENT CORPORATION ,  LEOPARDI, Rosario ,  ROIZMAN, Bernard

Inventor： ARCH DEVELOPMENT CORPORATION

IPC: C12N15/38

CPC classification number: C07K14/005 ,  A61K38/00 ,  A61K48/00 ,  C12N2710/16622

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 translation: 单纯疱疹病毒的ICP4蛋白在病毒基因的反式激活中起重要作用。 本发明公开了ICP4还具有抑制细胞凋亡的能力。 该功能似乎存在于与反式激活功能不同的功能区域中，如使用ICP4的温度敏感突变体在高温下的反式激活功能的研究所指出的。 还公开了使用ICP4或ICP4编码基因（例如α4基因）抑制凋亡的方法，抑制ICP4的细胞凋亡抑制功能的方法，以及用于产生重组蛋白质和治疗HSV感染的方法。