ArticleMolecular therapy : the journal of the American Society of Gene Therapy2007
Proteolytic disassembly is a critical determinant for reovirus oncolysis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
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- Human Melanoma and Glioblastoma Cells Express Cathepsins Supporting Reovirus Moscow Strain Infection.Viruses · 2024Article
- The Potential of Oncolytic Virotherapy in the Treatment of Head and Neck Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Oral reovirus reshapes the gut microbiome and enhances antitumor immunity in colon cancer.Nature communications · 2024Article
- The reovirus variant RP116 is oncolytic in immunocompetent models and generates reduced neutralizing antibodies to Type 3 Dearing.Molecular therapy. Oncology · 2024Article
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- Personalizing Oncolytic Virotherapy for Glioblastoma: In Search of Biomarkers for Response.Cancers · 2021Review
- Immunotherapy Resistance in Glioblastoma.Frontiers in genetics · 2021Review
- Past, Present and Future of Oncolytic Reovirus.Cancers · 2020Review
- Quantitative Proteome Responses to Oncolytic Reovirus in GM-CSF- and M-CSF-Differentiated Bone Marrow-Derived Cells.Journal of proteome research · 2020Article
- Combination Therapy with Reovirus and ATM Inhibitor Enhances Cell Death and Virus Replication in Canine Melanoma.Molecular therapy oncolytics · 2019Article
- Review
- Current understanding of reovirus oncolysis mechanisms.Oncolytic virotherapy · 2018Review
- New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy.Biologics : targets & therapy · 2018Review
- Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase.Molecular therapy oncolytics · 2017Article
- Baculovirus-assisted Reovirus Infection in Monolayer and Spheroid Cultures of Glioma cells.Scientific reports · 2017Article
- Review: Oncolytic virotherapy, updates and future directions.Oncotarget · 2017Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Mammalian ortheoreoviruses are currently being investigated as novel cancer therapeutics, but the cellular mechanisms that regulate susceptibility to reovirus oncolysis remain poorly understood. In this study, we present evidence that virion disassembly is a key determinant of reovirus oncolysis. To penetrate cell membranes and initiate infection, the outermost capsid proteins of reovirus must be proteolyzed to generate a disassembled particle called an infectious subviral particle (ISVP). In fibroblasts, this process is mediated by the endo/lysosomal proteases cathepsins B and L. We have analyzed the early events of infection in reovirus-susceptible and -resistant cells. We find that, in contrast to susceptible glioma cells and Ras-transformed NIH3T3 cells, reovirus-resistant cancer cells and untransformed NIH3T3 cells restrict virion uncoating and subsequent gene expression. Disassembly-restrictive cells support reovirus infection, as in vitro-generated ISVPs establish productive infection, and pretreatment with poly(I:C) does not prevent infection in cancer cells. We find that the level of active cathepsin B and L is increased in tumors and that disassembly-restrictive glioma cells support reovirus oncolysis when grown as a tumor in vivo. Together, these results provide a model in which proteolytic disassembly of reovirus is a critical determinant of susceptibility to reovirus oncolysis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.