Matrix Protein Mutations Contribute to Inefficient Induction of Apoptosis Leading to Persistent Infection of Human Neural Cells by Vesicular Stomatitis Virus

Desforges, Marc; Despars, Geneviève; Bérard, Stéphane; Gosselin, Myriam; McKenzie, Margie O.; Lyles, Douglas S.; Talbot, Pierre J.; Poliquin, Laurent

doi:10.1006/viro.2001.1329

Cited by 33 publications

(36 citation statements)

References 55 publications

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“…In addition, VSV matrix M protein has been shown to inhibit host cell gene expression and nuclear export of host mRNA via an association between M protein and Nup98, a host nuclear pore protein, with subsequent induction of apoptosis (Kopecky et al, 2001;Desforges et al, 2002;Kopecky and Lyles, 2003). The present results in HTLV-1-transformed MT-4 cells and in primary ATL demonstrate that VSV-induced apoptosis correlated with VSV replication, and that caspase-3 activation and subsequent apoptotic events involving Rho-GDI cleavage and DFF45 processing occurred only following VSV replication.…”

Section: Discussionmentioning

confidence: 99%

Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia

et al. 2005

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“…M is a small (202-amino-acid), multifunctional protein (25 kDa) that is responsible for the assembly and budding of virus particles (29,30,50) as well as for the regulation of the balance of virus transcription and replication (24). M also induces cell death in the related vesiculoviruses and fish rhabdoviruses (12,16,43,44). Taken together, these results suggest that apoptosis induced by the M protein is probably a common outcome of rhabdovirus infection.…”

mentioning

confidence: 93%

Lyssavirus Matrix Protein Induces Apoptosis by a TRAIL-Dependent Mechanism Involving Caspase-8 Activation

Kassis¹,

Larrous²,

Estaquier

et al. 2004

J Virol

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Lyssaviruses, which are members of the Rhabdoviridae family, induce apoptosis, which plays an important role in the neuropathogenesis of rabies. However, the mechanisms by which these viruses mediate neuronal apoptosis have not been elucidated. Here we demonstrate that the early induction of apoptosis in a model of lyssavirus-infected neuroblastoma cells involves a TRAIL-dependent pathway requiring the activation of caspase-8 but not of caspase-9 or caspase-10. The activation of caspase-8 results in the activation of caspase-3 and caspase-6, as shown by an increase in the cleavage of the specific caspase substrate in lyssavirus-infected cells. However, neither caspase-1 nor caspase-2 activity was detected during the early phase of infection. Lyssavirus-mediated cell death involves an interaction between TRAIL receptors and TRAIL, as demonstrated by experiments using neutralizing antibodies and soluble decoy TRAIL-R1/R2 receptors. We also demonstrated that the decapsidation and replication of lyssavirus are essential for inducing apoptosis, as supported by UV inactivation, cycloheximide treatment, and the use of bafilomycin A1 to inhibit endosomal acidification. Transfection of cells with the matrix protein induced apoptosis using pathways similar to those described in the context of viral infection. Furthermore, our data suggest that the matrix protein of lyssaviruses plays a major role in the early induction of TRAIL-mediated apoptosis by the release of a soluble, active form of TRAIL. In our model, Fas ligand (CD95L) appears to play a limited role in lyssavirus-mediated neuroblastoma cell death. Similarly, tumor necrosis factor alpha does not appear to play an important role.

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“…It also inhibits cellular translation (15) by modifying the initiation complex eIF4F through dephosphorylation of the initiation factors eIF4E and 4E-BP1 (10). Finally, it was also shown to participate in apoptosis induction (12,(23)(24)(25).…”

mentioning

confidence: 99%

“…G 5 , G 6 , G 5R , and G 6R were previously shown to possess a wild-type M protein (11) while still being able to inhibit cellular protein translation (15) without persisting in infected cells (12). These properties render them attractive candidates for oncolytic virotherapy studies.…”

mentioning

confidence: 99%

Mutations in the Glycoprotein of Vesicular Stomatitis Virus Affect Cytopathogenicity: Potential for Oncolytic Virotherapy

Janelle

Brassard

Lapierre

et al. 2011

J Virol

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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.

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Matrix Protein Mutations Contribute to Inefficient Induction of Apoptosis Leading to Persistent Infection of Human Neural Cells by Vesicular Stomatitis Virus

Cited by 33 publications

References 55 publications

Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia

Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia

Lyssavirus Matrix Protein Induces Apoptosis by a TRAIL-Dependent Mechanism Involving Caspase-8 Activation

Mutations in the Glycoprotein of Vesicular Stomatitis Virus Affect Cytopathogenicity: Potential for Oncolytic Virotherapy

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