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.
Yao
F
F
Brigham and Women's Hospital, and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA. FYao@RICS.BWH.Harvard.Edu
Eriksson
E
E
D000818:Animals; D000998:Antiviral Agents; D015139:Blotting, Southern; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D011995:Recombination, Genetic; D018741:Replication Origin; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; C034811:tetracycline resistance-encoding transposon repressor protein; C064565:UL9 protein, Human herpesvirus 1