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Viruses 2017, 9(10), 266; doi:10.3390/v9100266

Oncolytic Reovirus Infection Is Facilitated by the Autophagic Machinery

Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
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Received: 23 August 2017 / Revised: 18 September 2017 / Accepted: 20 September 2017 / Published: 21 September 2017
(This article belongs to the Section Animal Viruses)
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Abstract

Mammalian reovirus is a double-stranded RNA virus that selectively infects and lyses transformed cells, making it an attractive oncolytic agent. Despite clinical evidence for anti-tumor activity, its efficacy as a stand-alone therapy remains to be improved. The success of future trials can be greatly influenced by the identification and the regulation of the cellular pathways that are important for reovirus replication and oncolysis. Here, we demonstrate that reovirus induces autophagy in several cell lines, evident from the formation of Atg5-Atg12 complexes, microtubule-associated protein 1 light chain 3 (LC3) lipidation, p62 degradation, the appearance of acidic vesicular organelles, and LC3 puncta. Furthermore, in electron microscopic images of reovirus-infected cells, autophagosomes were observed without evident association with viral factories. Using UV-inactivated reovirus, we demonstrate that a productive reovirus infection facilitates the induction of autophagy. Importantly, knock-out cell lines for specific autophagy-related genes revealed that the expression of Atg3 and Atg5 but not Atg13 facilitates reovirus replication. These findings highlight a central and Atg13-independent role for the autophagy machinery in facilitating reovirus infection and contribute to a better understanding of reovirus-host interactions. View Full-Text
Keywords: mammalian orthoreovirus; replication; autophagy machinery; knockout; oncolysis mammalian orthoreovirus; replication; autophagy machinery; knockout; oncolysis
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MDPI and ACS Style

Kemp, V.; Dautzenberg, I.J.C.; Limpens, R.W.; van den Wollenberg, D.J.M.; Hoeben, R.C. Oncolytic Reovirus Infection Is Facilitated by the Autophagic Machinery. Viruses 2017, 9, 266.

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