title: Mutations in the glycoprotein of vesicular stomatitis virus affect cytopathogenicity: potential for oncolytic virotherapy.
abstract: 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.
authors.affiliation: Immunovirology Laboratory, Institut National de la Recherche Scientifique, INRS-Institut Armand-Frappier, Laval, Quebec, Canada H7V 1B7.
authors.forename: Valérie
authors.initials: V
authors.lastname: Janelle
authors.forename: Frédérick
authors.initials: F
authors.lastname: Brassard
authors.forename: Pascal
authors.initials: P
authors.lastname: Lapierre
authors.forename: Alain
authors.initials: A
authors.lastname: Lamarre
authors.forename: Laurent
authors.initials: L
authors.lastname: Poliquin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D007739:L Cells; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins