Saari Heikki, Turunen Tiia, Lõhmus Andres, Turunen Mikko, Jalasvuori Matti, Butcher Sarah J, Ylä-Herttuala Seppo, Viitala Tapani, Cerullo Vincenzo, Siljander Pia R M, Yliperttula Marjo
Division of Pharmaceutical Biosciences and Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
J Extracell Vesicles. 2020 Apr 17;9(1):1747206. doi: 10.1080/20013078.2020.1747206. eCollection 2020.
Extracellular vesicles (EVs) have been showcased as auspicious candidates for delivering therapeutic cargo, including oncolytic viruses for cancer treatment. Delivery of oncolytic viruses in EVs could provide considerable advantages, hiding the viruses from the immune system and providing alternative entry pathways into cancer cells. Here we describe the formation and viral cargo of EVs secreted by cancer cells infected with an oncolytic adenovirus (IEVs, infected cell-derived EVs) as a function of time after infection. IEVs were secreted already before the lytic release of virions and their structure resembled normally secreted EVs, suggesting that they were not just apoptotic fragments of infected cells. IEVs were able to carry the viral genome and induce infection in other cancer cells. As such, the role of EVs in the life cycle of adenoviruses may be an important part of a successful infection and may also be harnessed for cancer- and gene therapy.
细胞外囊泡（EVs）已被证明是递送治疗性物质的理想候选者，包括用于癌症治疗的溶瘤病毒。将溶瘤病毒包裹在EVs中递送可带来诸多显著优势，既能使病毒躲避免疫系统，又能提供进入癌细胞的替代途径。在此，我们描述了感染溶瘤腺病毒的癌细胞分泌的EVs（感染细胞衍生的EVs，即IEVs）的形成及病毒载量随感染后时间的变化情况。IEVs在病毒粒子裂解释放之前就已分泌，其结构类似于正常分泌的EVs，这表明它们并非仅仅是感染细胞的凋亡碎片。IEVs能够携带病毒基因组并在其他癌细胞中引发感染。因此，EVs在腺病毒生命周期中的作用可能是成功感染的重要组成部分，也可用于癌症和基因治疗。
