Oncolytic Replication of E1b-Deleted Adenoviruses.
Oncolytic Replication of E1b-Deleted Adenoviruses.
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DOI：
10.3390/v7112905
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发表时间：
2015-11-06
期刊：
影响因子：
--
通讯作者：
Zhou HS
中科院分区：
文献类型：
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作者：
Cheng PH;Wechman SL;McMasters KM;Zhou HS
各种病毒已被研究和开发用于溶瘤病毒治疗。在病毒治疗中，在肿瘤内注射中使用相对少量的病毒优先在癌细胞中复制和溶解，导致扩增的病毒颗粒释放，将感染扩散到周围的肿瘤细胞并减少肿瘤肿块。腺病毒（Ads）由于其感染效能、高滴度、安全性、易基因修饰和充分研究的复制特性而最常用于溶瘤病毒治疗。删除E1b55K的广告优先在癌细胞中复制并破坏癌细胞，并已用于多项临床试验。H101是e1b55k缺失的ad之一，作为首个获批的病毒治疗剂已被用于治疗晚期癌症。然而，e1b缺失的Ads在癌细胞中选择性复制的机制尚不清楚。本文将重点讨论E1B55K缺失Ads溶瘤复制的三种潜在分子机制。这些机制基于病毒E1B55K蛋白的功能，这些功能与p53抑制、病毒mRNA晚期输出和细胞周期破坏有关。
Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads) are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viral mRNA export, and cell cycle disruption.