Title |
Enhanced susceptibility of cancer cells to oncolytic rhabdo-virotherapy by expression of Nodamura virus protein B2 as a suppressor of RNA interference
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Published in |
Journal for Immunotherapy of Cancer, June 2018
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DOI | 10.1186/s40425-018-0366-2 |
Pubmed ID | |
Authors |
Donald Bastin, Amelia S. Aitken, Adrian Pelin, Larissa A. Pikor, Mathieu J. F. Crupi, Michael S. Huh, Marie-Claude Bourgeois-Daigneault, John C. Bell, Carolina S. Ilkow |
Abstract |
Antiviral responses are barriers that must be overcome for efficacy of oncolytic virotherapy. In mammalian cells, antiviral responses involve the interferon pathway, a protein-signaling cascade that alerts the immune system and limits virus propagation. Tumour-specific defects in interferon signaling enhance viral infection and responses to oncolytic virotherapy, but many human cancers are still refractory to oncolytic viruses. Given that invertebrates, fungi and plants rely on RNA interference pathways for antiviral protection, we investigated the potential involvement of this alternative antiviral mechanism in cancer cells. Here, we detected viral genome-derived small RNAs, indicative of RNAi-mediated antiviral responses, in human cancer cells. As viruses may encode suppressors of the RNA interference pathways, we engineered an oncolytic vesicular stomatitis virus variant to encode the Nodamura virus protein B2, a known inhibitor of RNAi-mediated immune responses. B2-expressing oncolytic virus showed enhanced viral replication and cytotoxicity, impaired viral genome cleavage and altered microRNA processing in cancer cells. Our data establish the improved therapeutic potential of our novel virus which targets the RNAi-mediated antiviral defense of cancer cells. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 3 | 60% |
Unknown | 2 | 40% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 40% |
Science communicators (journalists, bloggers, editors) | 2 | 40% |
Practitioners (doctors, other healthcare professionals) | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 33 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 24% |
Student > Ph. D. Student | 5 | 15% |
Student > Bachelor | 4 | 12% |
Student > Doctoral Student | 3 | 9% |
Other | 2 | 6% |
Other | 3 | 9% |
Unknown | 8 | 24% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 8 | 24% |
Medicine and Dentistry | 6 | 18% |
Immunology and Microbiology | 6 | 18% |
Agricultural and Biological Sciences | 3 | 9% |
Chemical Engineering | 1 | 3% |
Other | 0 | 0% |
Unknown | 9 | 27% |