Guedan S, Gros A, Cascallo M, Vile R, Mercade E, Alemany R
Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
Gene Ther. 2008 Sep;15(17):1240-5. doi: 10.1038/gt.2008.94. Epub 2008 May 29.
Fusogenic membrane glycoproteins (FMGs) may enhance the cytotoxicity of conditionally replicative adenoviruses. However, expression at early stages of infection impairs virus replication. We have inserted the hyperfusogenic form of the gibbon ape leukemia virus (GALV) envelope glycoprotein as a new splice unit of the major late promoter (MLP) to generate a replication-competent adenovirus expressing this protein. At high multiplicity of infection (MOI), this virus replicated efficiently forming clumps of fused cells and showing a faster release. In contrast, at low MOI, infected cells formed syncytia where only one nucleus contained virus DNA, decreasing total virus production but increasing cytotoxicity.
融合性膜糖蛋白(FMGs)可能增强条件性复制腺病毒的细胞毒性。然而,在感染早期表达会损害病毒复制。我们已将长臂猿白血病病毒(GALV)包膜糖蛋白的高融合形式作为主要晚期启动子(MLP)的新剪接单元插入,以产生表达该蛋白的具有复制能力的腺病毒。在高感染复数(MOI)时,这种病毒高效复制,形成融合细胞团并显示出更快的释放。相比之下,在低MOI时,受感染细胞形成多核巨细胞,其中只有一个细胞核含有病毒DNA,这降低了病毒总产量但增加了细胞毒性。