Open AccessBovine Herpesvirus Tegument Protein VP22 Enhances Thymidine Kinase/Ganciclovir Suicide Gene Therapy for Neuroblastomas Compared to Herpes Simplex Virus VP22
Author(s) -
Zhaohua Qiu,
Jerome S. Harms,
Jie Zhu,
Gary A. Splitter
Publication year - 2004
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.78.8.4224-4233.2004
Subject(s) - ganciclovir , biology , herpes simplex virus , thymidine kinase , suicide gene , transfection , genetic enhancement , in vivo , virology , cytotoxicity , microbiology and biotechnology , cell culture , in vitro , virus , gene , cancer research , human cytomegalovirus , biochemistry , genetics
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.