Immunovirology Laboratory, Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Quebec, Canada H7V 1B7.
J Virol. 2011 Jul;85(13):6513-20. doi: 10.1128/JVI.02484-10. Epub 2011 May 11.
Vesicular stomatitis virus (VSV) has been widely used to characterize cellular processes, viral resistance, and cytopathogenicity. Recently, VSV has also been used for oncolytic virotherapy due to its capacity to selectively lyse tumor cells. Mutants of the matrix (M) protein of VSV have generally been preferred to the wild-type virus for oncolysis because of their ability to induce type I interferon (IFN) despite causing weaker cytopathic effects. However, due to the large variability of tumor types, it is quite clear that various approaches and combinations of multiple oncolytic viruses will be needed to effectively treat most cancers. With this in mind, our work focused on characterizing the cytopathogenic profiles of four replicative envelope glycoprotein (G) VSV mutants. In contrast to the prototypic M mutant, VSV G mutants are as efficient as wild-type virus at inhibiting cellular transcription and host protein translation. Despite being highly cytopathic, the mutant G(6R) triggers type I interferon secretion as efficiently as the M mutant. Importantly, most VSV G mutants are more effective at killing B16 and MC57 tumor cells in vitro than the M mutant or wild-type virus through apoptosis induction. Taken together, our results demonstrate that VSV G mutants retain the high cytopathogenicity of wild-type VSV, with G(6R) inducing type I IFN secretion at levels similar to that of the M mutant. VSV G protein mutants could therefore prove to be highly valuable for the development of novel oncolytic virotherapy strategies that are both safe and efficient for the treatment of various types of cancer.
水疱性口炎病毒（VSV）已被广泛用于研究细胞过程、病毒抗性和细胞病变作用。最近，由于其选择性裂解肿瘤细胞的能力，VSV 也被用于溶瘤病毒治疗。VSV 基质（M）蛋白的突变体通常比野生型病毒更适合用于溶瘤，因为它们能够诱导 I 型干扰素（IFN），尽管它们引起的细胞病变作用较弱。然而，由于肿瘤类型的巨大变异性，很明显，需要采用各种方法和多种溶瘤病毒的组合，才能有效地治疗大多数癌症。考虑到这一点，我们的工作重点是表征四种复制包膜糖蛋白（G）VSV 突变体的细胞病变特征。与典型的 M 突变体不同，VSV G 突变体在抑制细胞转录和宿主蛋白翻译方面与野生型病毒一样有效。尽管具有高度的细胞病变作用，但突变体 G(6R) 引发 I 型干扰素分泌的效率与 M 突变体一样高。重要的是，大多数 VSV G 突变体通过诱导细胞凋亡，在体外比 M 突变体或野生型病毒更有效地杀死 B16 和 MC57 肿瘤细胞。总之，我们的研究结果表明，VSV G 突变体保留了野生型 VSV 的高细胞病变作用，G(6R) 诱导 I 型 IFN 分泌的水平与 M 突变体相似。因此，VSV G 蛋白突变体可能成为开发新型溶瘤病毒治疗策略的重要工具，这些策略对治疗各种类型的癌症既安全又有效。
