Replication and Oncolytic Activity of an Avian Orthoreovirus in Human Hepatocellular Carcinoma Cells.

Autor: Kozak RA; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. rob.kozak@gmail.com., Hattin L; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. larissa.hattin@medportal.ca., Biondi MJ; Sandra Rotman Centre for Global Health, University of Toronto, Toronto, ON M5G 1L7, Canada. mia.biondi@mail.mcgill.ca., Corredor JC; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. corredor@uoguelph.ca., Walsh S; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. scott.walsh22@gmail.com., Xue-Zhong M; Multi-Organ Transplant Program, Department of Surgery, University of Toronto, Toronto General Hospital, Toronto, ON M5G 2C4, Canada. maxuezhong@hotmail.com., Manuel J; Multi-Organ Transplant Program, Department of Surgery, University of Toronto, Toronto General Hospital, Toronto, ON M5G 2C4, Canada. jmanuel@research.ca., McGilvray ID; Multi-Organ Transplant Program, Department of Surgery, University of Toronto, Toronto General Hospital, Toronto, ON M5G 2C4, Canada. Ian.McGilvray@uhn.on.ca., Morgenstern J; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. jason.d.morgenstern@gmail.com., Lusty E; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. evanlusty@gmail.com., Cherepanov V; Sandra Rotman Centre for Global Health, University of Toronto, Toronto, ON M5G 1L7, Canada. vera.cherepanov@uhn.ca., McBey BA; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. bmcbey@uoguelph.ca., Leishman D; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. dleishma@uoguelph.ca., Feld JJ; Sandra Rotman Centre for Global Health, University of Toronto, Toronto, ON M5G 1L7, Canada. Jordan.feld@uhn.ca., Bridle B; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. bbridle@uoguelph.ca., Nagy É; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. enagy@uoguelph.ca.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2017 Apr 24; Vol. 9 (4). Date of Electronic Publication: 2017 Apr 24.
DOI: 10.3390/v9040090
Abstrakt: Oncolytic viruses are cancer therapeutics with promising outcomes in pre-clinical and clinical settings. Animal viruses have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. We isolated an avian orthoreovirus (ARV-PB1), and tested it against a panel of hepatocellular carcinoma cells. We found that ARV-PB1 replicated well and induced strong cytopathic effects. It was determined that one mechanism of cell death was through syncytia formation, resulting in apoptosis and induction of interferon stimulated genes (ISGs). As hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma worldwide, we investigated the effect of ARV-PB1 against cells already infected with this virus. Both HCV replicon-containing and infected cells supported ARV-PB1 replication and underwent cytolysis. Finally, we generated in silico models to compare the structures of human reovirus- and ARV-PB1-derived S1 proteins, which are the primary targets of neutralizing antibodies. Tertiary alignments confirmed that ARV-PB1 differs from its human homolog, suggesting that immunity to human reoviruses would not be a barrier to its use. Therefore, ARV-PB1 can potentially expand the repertoire of oncolytic viruses for treatment of human hepatocellular carcinoma and other malignancies.
Databáze: MEDLINE
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