Imaging immediate-early and strict-late promoter activity during oncolytic herpes simplex virus type 1 infection and replication in tumors.
Imaging immediate-early and strict-late promoter activity during oncolytic herpes simplex virus type 1 infection and replication in tumors.
复制标题
溶瘤单纯疱疹病毒 1 型感染和肿瘤复制过程中立即早期和严格晚期启动子活性的成像。
DOI：
10.1038/sj.gt.3302831
复制
发表时间：
2006
期刊：
影响因子：
5.1
通讯作者：
Saeki,Y
中科院分区：
文献类型：
--
作者：
Yamamoto,S;Deckter,LA;Kasai,K;Chiocca,EA;Saeki,Y
越来越多的溶瘤病毒已被开发和研究用于癌症治疗。为了响应溶瘤病毒疗法的非侵入性监测和成像的需要，已经报道了几种不同的方法，包括基于正电子发射断层扫描的方法、使用分泌的标记肽的方法和基于光学成像的方法。在这些模式中，我们利用基于生物发光测定/成像系统来确定生产性病毒感染的动力学和动力学。单纯疱疹病毒1型（HSV-1）的复制周期被三类病毒基因的时间级联打断：即早期（IE），早期（E）和晚期（L）基因。产生在IE 4/5或严格晚期gC启动子的控制下表达萤火虫荧光素酶的UL 39和γ 134.5缺失的复制条件HSV-1突变体。在培养的细胞和小鼠肿瘤模型中检查这些溶瘤病毒。IE启动子和严格晚期启动子介导的荧光素酶表达被证实分别指示病毒感染和复制。将严格晚期启动子驱动的荧光素酶盒并入溶瘤HSV-1载体将可用于在临床前肿瘤治疗研究中评估肿瘤溶瘤。
An increasing number of oncolytic viruses have been developed and studied for cancer therapy. In response to needs for non-invasive monitoring and imaging of oncolytic virotherapy, several different approaches, including a positron emission tomography-based method, a method using secreted marker peptides, and optical imaging-based methods, have been reported. Among these modalities, we utilized the luciferase-based bioluminescent assay/imaging systems to determine the kinetics and dynamics of a productive viral infection. The replication cycle of herpes simplex virus type 1 (HSV-1) is punctuated by a temporal cascade of three classes of viral genes: immediate-early (IE), early (E) and late (L) genes. U L 39-and γ 1 34.5-deleted, replication-conditional HSV-1 mutants that express firefly luciferase under the control of the IE4/5 or strict-late gC promoters were generated. These oncolytic viruses were examined in cultured cells and a mouse tumor model. IE promoter-and strict-late promoter-mediated luciferase expression was confirmed to indicate viral infection and replication, respectively. Incorporation of a strict-late promoter-driven luciferase cassette into oncolytic HSV-1 vectors would be useful for assessing tumor oncolysis in preclinical tumor treatment studies.