A novel anti-herpes simplex virus type 1-specific herpes simplex virus type 1 recombinant

A recombinant herpes simplex virus (HSV) capable of inhibiting its own replication as well as the replication of wild-type virus would have greatly increased safety as a general purpose vector for in vivo gene transfer, antitumor therapy, and viral vaccine against HSV infection. By using a tetracycline repressor (tetR)-mediated HSV-1 viral replication switch [Yao and Eriksson (1999). Hum. Gene Ther. 10, 419-427], we have generated a novel anti-HSV-1-specific HSV-1 recombinant (CJ83193) that expresses a trans-dominant negative HSV-1 UL9 origin-binding protein, UL9-C535C. The de novo synthesis of CJ83193 can be suppressed by UL9-C535C by at least 1 x 10(6)-fold in non-tetR-expressing cells, and is subject to tetracycline regulation over a range of four to five orders of magnitude in a tetR-expressing osteosarcoma line. In particular, the UL9-C535C peptides expressed from the CJ83193 genome can inhibit the replication of wild-type HSV-1 by 100- to 200-fold in single-step growth assays. The construction of CJ83193 creates a new general strategy for developing recombinant viral vectors able to function as an intracellular therapy against wild-type viral infections.