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Viruses 2017, 9(4), 90; doi:10.3390/v9040090

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

1
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
2
Sandra Rotman Centre for Global Health, University of Toronto, Toronto, ON M5G 1L7, Canada
3
Multi-Organ Transplant Program, Department of Surgery, University of Toronto, Toronto General Hospital, Toronto, ON M5G 2C4, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 11 March 2017 / Revised: 19 April 2017 / Accepted: 19 April 2017 / Published: 24 April 2017
(This article belongs to the Section Animal Viruses)
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Abstract

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. View Full-Text
Keywords: avian orthoreovirus; hepatocellular carcinoma; hepatitis C virus; oncolytic virus; syncytia avian orthoreovirus; hepatocellular carcinoma; hepatitis C virus; oncolytic virus; syncytia
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Kozak, R.A.; Hattin, L.; Biondi, M.J.; Corredor, J.C.; Walsh, S.; Xue-Zhong, M.; Manuel, J.; McGilvray, I.D.; Morgenstern, J.; Lusty, E.; Cherepanov, V.; McBey, B.-A.; Leishman, D.; Feld, J.J.; Bridle, B.; Nagy, É. Replication and Oncolytic Activity of an Avian Orthoreovirus in Human Hepatocellular Carcinoma Cells. Viruses 2017, 9, 90.

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