Abstract：
Oncolytic virotherapy is an emerging treatment option for numerous cancers, with several virus families currently being evaluated in clinical trials. More specifically, vaccine-strain measles virus has arisen as a promising candidate for the treatment of different tumour types in several early clinical trials. Replicating viruses, and especially RNA viruses without proofreading polymerases, can rapidly adapt to varying environments by selecting quasispecies with advantageous genetic mutations. Subsequently, these genetic alterations could potentially weaken the safety profile of virotherapy. In this study, we demonstrate that, following an extended period of virus replication in producer or cancer cell lines, the quasispecies consensus sequence of vaccine strain-derived measles virus accrues a remarkably small number of mutations throughout the nonsegmented negative-stranded RNA genome. Interestingly, we detected a nonrandom distribution of genetic alterations within the genome, with an overall decreasing frequency of mutations from the 3\' genome start to its 5\' end. Comparing the serially passaged viruses to the parental virus on producer cells, we found that the acquired consensus mutations did not drastically change viral replication kinetics or cytolytic potency. Collectively, our data corroborate the genomic stability and excellent safety profile of oncolytic measles virus, thus supporting its continued development and clinical translation as a promising viro-immunotherapeutic.
摘要：
溶瘤病毒疗法是许多癌症的新兴治疗选择。目前正在临床试验中评估几个病毒家族。更具体地说,在几项早期临床试验中，疫苗株麻疹病毒已成为治疗不同肿瘤类型的有希望的候选者。复制病毒,尤其是没有校对聚合酶的RNA病毒，可以通过选择具有优势基因突变的准种来快速适应变化的环境。随后，这些基因改变可能会削弱病毒治疗的安全性.在这项研究中,我们证明，在生产者或癌细胞系中病毒复制的延长期之后，疫苗株来源的麻疹病毒的准种共有序列在整个非节段负链RNA基因组中产生的突变数量非常少.有趣的是,我们检测到基因组中遗传改变的非随机分布，从3'基因组开始到5'末端的突变频率总体下降。将连续传代的病毒与生产细胞上的亲本病毒进行比较，我们发现,获得性共有突变并没有显著改变病毒复制动力学或溶细胞效能.总的来说，我们的数据证实了溶瘤麻疹病毒的基因组稳定性和优异的安全性，从而支持其作为一种有前途的病毒免疫治疗的持续发展和临床翻译。
