Qiu Zhaohua, Harms Jerome S, Zhu Jun, Splitter Gary A
Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
J Virol. 2004 Apr;78(8):4224-33. doi: 10.1128/jvi.78.8.4224-4233.2004.
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.
疱疹病毒被膜蛋白VP22可增强治疗性蛋白在基因治疗中的效果，如胸苷激酶（tk）和p53；然而，其机制尚不清楚或存在争议。在本研究中，构建了携带牛疱疹病毒1型（BHV-1）VP22（BVP22）或单纯疱疹病毒1型（HSV-1）VP22（HVP22）以及马疱疹病毒4型（EHV-4）tk（Etk）的哺乳动物表达载体，以便通过体外和体内的更昔洛韦（GCV）细胞毒性试验及无创生物发光成像，评估和比较BVP22和HVP22增强Etk/GCV自杀基因疗法治疗神经母细胞瘤的治疗潜力。在体外和体内，与HVP22相比，BVP22增强了Etk/GCV的细胞毒性。然而，利用亲代细胞和稳定转染细胞混合物的试验表明，仅在转染细胞中检测到增强作用。因此，在该肿瘤系统中，BVP22和HVP22在Etk/GCV自杀基因治疗中的治疗潜力并非由于VP22将Etk递送至周围细胞，而是可能由于细胞内效应增强。
