bioRxiv preprint doi: https://doi.org/10.1101/569301; this version posted March 6, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Genetic Polymorphisms and Molecular Mechanisms Mediating Oncolytic Potency of Reovirus Strains 2 Adil Mohamed1, Derek R. Clements2, Prathyusha Konda2, Shashi A. Gujar2,3, Patrick W. Lee2, James R. Smiley1, 3 Maya Shmulevitz1* 4 5 6 1Department of Medical Microbiology and Immunology, Li Ka Shing Institute of Virology, University of Alberta, 7 Edmonton, Alberta, Canada. 8 2Department of Pathology and Department of Microbiology and Immunology, Dalhousie University, Halifax, 9 Nova Scotia, Canada. 10 3Centre for Innovative and Collaborative Health Systems Research, IWK Health Centre, Halifax, Nova Scotia, 11 Canada. 12 13 Running Head: Reovirus Strain Specific Oncolysis 14 15 *Correspondence:
[email protected] 16 17 1 bioRxiv preprint doi: https://doi.org/10.1101/569301; this version posted March 6, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 18 ABSTRACT 19 The Dearing strain of Mammalian orthoreovirus (T3D) is undergoing clinical trials as an oncolytic 20 virotherapeutic agent. In this study, a comprehensive phenotypic and genetic comparison of T3D virus stocks 21 from various laboratories and commercial sources revealed that T3D laboratory strains differ substantially in their 22 oncolytic activities in vitro and in vivo. Superior replication of the most-oncolytic T3D lab strain was attributed to 23 several mechanistic advantages: virus-cell binding, viral RNA transcriptase activity, viral inclusion morphology, 24 and differential activation of RIG-I versus NFκB-dependent signalling pathways.