title: Bovine herpesvirus tegument protein VP22 enhances thymidine kinase/ganciclovir suicide gene therapy for neuroblastomas compared to herpes simplex virus VP22.
abstract: Herpesvirus tegument protein VP22 can enhance the effect of therapeutic proteins in gene therapy, such as thymidine kinase (tk) and p53; however, the mechanism is unclear or controversial. In this study, mammalian expression vectors carrying bovine herpesvirus 1 (BHV-1) VP22 (BVP22) or herpes simplex virus type 1 (HSV-1) VP22 (HVP22) and equine herpesvirus type 4 (EHV-4) tk (Etk) were constructed in order to evaluate and compare the therapeutic potentials of BVP22 and HVP22 to enhance Etk/ganciclovir (Etk/GCV) suicide gene therapy for neuroblastomas by GCV cytotoxicity assays and noninvasive bioluminescent imaging in vitro and in vivo. BVP22 enhanced Etk/GCV cytotoxicity compared to that with HVP22 both in vitro and in vivo. However, assays utilizing a mixture of parental and stably transfected cells indicated that the enhancement was detected only in transfected cells. Thus, the therapeutic potential of BVP22 and HVP22 in Etk/GCV suicide gene therapy in this tumor system is not due to VP22 delivery of Etk into surrounding cells but rather is likely due to an enhanced intracellular effect.
authors.affiliation: Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Qiu
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Harms
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Gary A
authors.initials: GA
authors.lastname: Splitter
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D002417:Cattle; D045744:Cell Line, Tumor; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D023141:Herpesvirus 4, Equid / Q000201:enzymology / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009447:Neuroblastoma / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; C434023:tegument protein VP22, bovine herpesvirus 1; D013937:Thymidine Kinase; D015774:Ganciclovir